PMC:7572937 / 29338-38248 JSONTXT

{"project":"MyTest","denotations":[{"id":"33082511-27317359-29997622","span":{"begin":361,"end":362},"obj":"27317359"},{"id":"33082511-28923364-29997623","span":{"begin":680,"end":682},"obj":"28923364"},{"id":"33082511-28923364-29997624","span":{"begin":942,"end":944},"obj":"28923364"},{"id":"33082511-591063-29997625","span":{"begin":1315,"end":1317},"obj":"591063"},{"id":"33082511-1999504-29997626","span":{"begin":1318,"end":1320},"obj":"1999504"},{"id":"33082511-1999504-29997627","span":{"begin":1445,"end":1447},"obj":"1999504"},{"id":"33082511-10534074-29997628","span":{"begin":1553,"end":1555},"obj":"10534074"},{"id":"33082511-11559706-29997628","span":{"begin":1553,"end":1555},"obj":"11559706"},{"id":"33082511-12747452-29997628","span":{"begin":1553,"end":1555},"obj":"12747452"},{"id":"33082511-12595898-29997628","span":{"begin":1553,"end":1555},"obj":"12595898"},{"id":"33082511-17927965-29997628","span":{"begin":1553,"end":1555},"obj":"17927965"},{"id":"33082511-10534074-29997629","span":{"begin":1849,"end":1851},"obj":"10534074"},{"id":"33082511-11559706-29997630","span":{"begin":1963,"end":1965},"obj":"11559706"},{"id":"33082511-12747452-29997631","span":{"begin":1966,"end":1968},"obj":"12747452"},{"id":"33082511-12747452-29997632","span":{"begin":2049,"end":2052},"obj":"12747452"},{"id":"33082511-12595898-29997633","span":{"begin":2196,"end":2198},"obj":"12595898"},{"id":"33082511-28923364-29997634","span":{"begin":2623,"end":2625},"obj":"28923364"},{"id":"33082511-28442746-29997635","span":{"begin":3057,"end":3059},"obj":"28442746"},{"id":"33082511-28361884-29997636","span":{"begin":3466,"end":3468},"obj":"28361884"},{"id":"33082511-29684359-29997637","span":{"begin":3876,"end":3878},"obj":"29684359"},{"id":"33082511-21548792-29997638","span":{"begin":5118,"end":5120},"obj":"21548792"},{"id":"33082511-16723446-29997638","span":{"begin":5118,"end":5120},"obj":"16723446"},{"id":"33082511-27072607-29997638","span":{"begin":5118,"end":5120},"obj":"27072607"},{"id":"33082511-31272712-29997638","span":{"begin":5118,"end":5120},"obj":"31272712"},{"id":"33082511-21228377-29997638","span":{"begin":5118,"end":5120},"obj":"21228377"},{"id":"33082511-23012360-29997638","span":{"begin":5118,"end":5120},"obj":"23012360"},{"id":"33082511-31272712-29997639","span":{"begin":5305,"end":5307},"obj":"31272712"},{"id":"33082511-23645879-29997640","span":{"begin":5308,"end":5311},"obj":"23645879"},{"id":"33082511-25277308-29997640","span":{"begin":5308,"end":5311},"obj":"25277308"},{"id":"33082511-24790856-29997640","span":{"begin":5308,"end":5311},"obj":"24790856"},{"id":"33082511-30419240-29997640","span":{"begin":5308,"end":5311},"obj":"30419240"},{"id":"33082511-21548792-29997641","span":{"begin":5842,"end":5845},"obj":"21548792"},{"id":"33082511-16723446-29997642","span":{"begin":5846,"end":5848},"obj":"16723446"},{"id":"33082511-21548792-29997643","span":{"begin":6216,"end":6218},"obj":"21548792"},{"id":"33082511-25146982-29997644","span":{"begin":6332,"end":6335},"obj":"25146982"},{"id":"33082511-29643724-29997645","span":{"begin":7108,"end":7112},"obj":"29643724"},{"id":"33082511-16723446-29997646","span":{"begin":7263,"end":7265},"obj":"16723446"},{"id":"33082511-24790856-29997647","span":{"begin":7392,"end":7395},"obj":"24790856"},{"id":"33082511-30419240-29997648","span":{"begin":7989,"end":7992},"obj":"30419240"},{"id":"33082511-27072607-29997649","span":{"begin":8099,"end":8102},"obj":"27072607"},{"id":"33082511-28892824-29997650","span":{"begin":8103,"end":8106},"obj":"28892824"},{"id":"33082511-27072607-29997651","span":{"begin":8255,"end":8257},"obj":"27072607"},{"id":"33082511-28892824-29997652","span":{"begin":8422,"end":8425},"obj":"28892824"},{"id":"33082511-30419240-29997653","span":{"begin":8906,"end":8909},"obj":"30419240"}],"namespaces":[{"prefix":"_base","uri":"https://www.uniprot.org/uniprot/testbase"},{"prefix":"UniProtKB","uri":"https://www.uniprot.org/uniprot/"},{"prefix":"uniprot","uri":"https://www.uniprot.org/uniprotkb/"}],"text":"FPRs in other mucosal surfaces\n\nFPRs in the oral cavity\nThe oral cavity is the first site at which external substances enter before proceeding into the GI tract and respiratory tract. Many kinds of stimulants, such as food, allergens, and pathogens, enter the oral cavity. The oral cavity is the site with the second largest microbiota after the large intestine4. Because the fundamental role of the mouth is eating, there is constant mastication and physical stimulation. The oral cavity comprises several barrier surfaces, including the lining mucosa, masticatory mucosa, tongue mucosa, and gingival crevice. These surfaces are kept moist by saliva and gingival crevicular fluid80. The immunological feature of the oral cavity is that both mucosal immunity (soluble IgA) and systemic immunity (plasma IgG) protect this site81. Because of the complex immunological conditions, all immune cell types are resident and active in the oral cavity80.\nReports on FPRs in the oral cavity have focused on very narrow aspects: reports on FPR1 have focused on periodontitis, and reports on FPR2 have focused on submandibular gland and saliva production. Periodontitis is a disease caused by gingival infection. Since the 1970s, it has been well known that neutrophils from periodontitis patients have defective FPR1 signaling82,83. In particular, neutrophils from juvenile periodontitis patients showed decreased migratory ability towards fMLP but not C5a83. From these findings, researchers uncovered genetic variations in the FPR1 gene in periodontitis patients84–88. Although the type of periodontitis was different, the genetic variations in FPR1 from periodontitis patients had a common feature; the mutations caused the receptor to malfunction. The FPR1-329T\u003eC and FPR1-378C\u003eG variants cause F110S and C126W amino acid sequence alterations, respectively84. These mutations are associated with decreased migratory ability towards fMLP and defects in G protein coupling85,86. In particular, mutation of amino acid 110 affects the surface expression of FPR186. Other mutations that occur are R190W and N192K, which change the extracellular loop structure of FPR1 and decrease its ligand binding affinity87.\nStudies on the role of FPR2 have focused on the submandibular gland. The submandibular gland is one of the major salivary glands located under the floor of the mouth. Saliva is a watery fluid produced from salivary glands that contains various innate antimicrobial molecules, such as immunoglobulins, lysozyme, and lactoferrin. Decreased saliva production or the absence of saliva increases susceptibility to oral infection80. FPR2 and its ligand RvD1 reduce immune responses in the salivary glands. Fpr2 knockout mice were found to show an enhanced immune response in the salivary gland in an LPS challenge model. These knockout mice exhibited abnormalities such as increased immune cell infiltration in the salivary gland, upregulation of inflammatory cytokines, decreased saliva production, increased apoptosis, and alterations in tight junction proteins89. RvD1 activates FPR2 on the salivary glands and helps to maintain salivary gland integrity and to inhibit apoptosis and TNF-α-mediated inflammation90,91.\nSjogren syndrome (SS) is a chronic autoimmune disease that decreases the function of exocrine glands. As a result, the production of tears and saliva decreases. One study focused on the effect of RvD1 on NOD/ShiLtJ mice, whose phenotype mimics human SS92. RvD1 activates FPR2 expressed on submandibular gland cells, showing a preventive effect on the onset of disease by improving secretory function, decreasing proinflammatory molecule expression, and increasing anti-inflammatory molecule expression and M2 macrophage polarization. Interestingly, old female Fpr2 knockout mice show symptoms similar to those of SS, such as reduced salivary flow and weight loss93. Fpr2 knockout mice have an increased CD20+ B cell population and enhanced autoantibody production in the submandibular glands. This observation implies that FPR2 maintains the functional status of salivary glands by shaping adaptive immunity and regulating the inflammatory response intensity.\n\nFPRs in the eye\nThe eye is an organ of the visual system. The structure of the eye evolved anatomically and immunologically to protect visual function81. Significantly, the exterior surface of the eye is in direct contact with the external environment and encounters an enormous amount of immunogens. The immune response in the eye is strictly regulated to maintain the transparency of the cornea. The ocular mucosal surface includes the cornea and the conjunctiva. Tear film protects these mucosal surfaces, and neural inputs from the cornea and conjunctiva regulate the production of tears. Tears contain various protective substances, such as mucin produced by goblet cells and immunoglobulins produced by plasma cells81.\nFPRs are expressed on various cell types in the ocular region, such as corneal endothelial cells, corneal epithelial cells, conjunctival goblet cells, retinal microglia, retinal pigment cells, and lens epithelial cells94–99. Additionally, various FPR-related ocular pathologies exist, such as retinal degeneration, uveitis, polypoidal choroidal vasculopathy, corneal neovascularization, and ocular allergy97,100–103. However, here, we only discuss the role of FPRs in the cornea and conjunctiva as ocular mucosal surfaces. The cornea is located at the anterior aspect of the eye and passes light to the lens. The immune response in the cornea is unreactive compared to that in the conjunctiva, because inflammation of the cornea can affect its transparency104. FPR2 is expressed on the corneal endothelium and epithelium, and the functional activity of FPR2 in those regions has been indirectly confirmed by effects of the FPR2 antagonist WRW494,95. The cornea is a transplantable tissue, and there are several reports that the ligands of FPR2, including LXA4 and RvD1, can be beneficial during corneal transplantation. LXA4 promotes the proliferation of human corneal endothelial cells, and when added to Optisol-GS, which is the pretransplant storage fluid for corneas, LXA4 reduces corneal endothelial cell damage94. RvD1 reduces allograft mortality during corneal transplantation by regulating DC-mediated inflammatory responses105. Although RvD1 promotes corneal wound healing, it is not clear whether FPR2 mediates the effect of RvD1 in vivo.\nDiabetes is a representative metabolic disease with ocular complications. Diabetic patients show impaired corneal wound healing because of corneal epithelium and nerve defects. RvD1 can improve corneal epithelial regeneration in diabetic mice. RvD1 acts via the following mechanisms: increased expression of proliferation-related molecules (Ki67 and SIRT1), EGFR activation, decreased inflammatory cytokine (TNF-α, IL-1β) production, decreased expression of ROS-generating enzymes (NOX2 and NOX3), and upregulated expression of antioxidant genes (Nrf2, MnSOD, and HO-1). WRW4, the FPR2 antagonist, significantly blocks these various therapeutic effects of RvD1106. Another FPR2 ligand, LL-37, also promotes corneal epithelial cell migration in a PTX- and FPR2-sensitive manner and facilitates corneal wound healing95. Regarding SAA, the expression of Saa1,3 was increased with the expression of Fpr2 in a corneal neovascularization mouse model102. This pattern implies that SAA-FPR2 plays a role in this condition.\nThe conjunctiva is a mucosal tissue composed of three layers: the conjunctival epithelial layer, goblet cell layer, and lamina propria. The lamina propria is the site where immune cells reside and produces immunoregulatory factors. In the conjunctiva, several immune responses, such as antigen processing, cell-mediated immunity, and hypersensitivity, occur104. The conjunctiva exhibits basal expression of FPR1 and FPR2, and FPR1 and FPR2 expression is elevated in the setting of inflammation, such as in allergic conditions103. FPR2 is expressed on conjunctival goblet cells and increases mucin production by recognizing LXA4 and RvD196,107. Intracellular calcium influx is directly related to glycoconjugate secretion, and the LXA4-FPR2 axis can promote mucin secretion via calcium influx96. Various downstream signaling molecules of FPR2 affect calcium influx, which shows that FPR2 signaling and homeostasis of the ocular environment are closely related107.\nOne report addressed AnxA1 and FPRs in the case of ocular allergy. Upon the induction of allergic conjunctivitis in mice, FPR1 and FPR2 expression was increased. Interestingly, AnxA1 knockout mice showed a significant increase in FPR2 expression. AnxA1 is an anti-inflammatory mediator that decreases granulocyte infiltration and proinflammatory cytokine production in allergic conjunctivitis. These protective effects were diminished by treatment with Boc2, a pan-FPR antagonist103."}

{"project":"2_test","denotations":[{"id":"33082511-27317359-29997622","span":{"begin":361,"end":362},"obj":"27317359"},{"id":"33082511-28923364-29997623","span":{"begin":680,"end":682},"obj":"28923364"},{"id":"33082511-28923364-29997624","span":{"begin":942,"end":944},"obj":"28923364"},{"id":"33082511-591063-29997625","span":{"begin":1315,"end":1317},"obj":"591063"},{"id":"33082511-1999504-29997626","span":{"begin":1318,"end":1320},"obj":"1999504"},{"id":"33082511-1999504-29997627","span":{"begin":1445,"end":1447},"obj":"1999504"},{"id":"33082511-10534074-29997628","span":{"begin":1553,"end":1555},"obj":"10534074"},{"id":"33082511-11559706-29997628","span":{"begin":1553,"end":1555},"obj":"11559706"},{"id":"33082511-12747452-29997628","span":{"begin":1553,"end":1555},"obj":"12747452"},{"id":"33082511-12595898-29997628","span":{"begin":1553,"end":1555},"obj":"12595898"},{"id":"33082511-17927965-29997628","span":{"begin":1553,"end":1555},"obj":"17927965"},{"id":"33082511-10534074-29997629","span":{"begin":1849,"end":1851},"obj":"10534074"},{"id":"33082511-11559706-29997630","span":{"begin":1963,"end":1965},"obj":"11559706"},{"id":"33082511-12747452-29997631","span":{"begin":1966,"end":1968},"obj":"12747452"},{"id":"33082511-12747452-29997632","span":{"begin":2049,"end":2052},"obj":"12747452"},{"id":"33082511-12595898-29997633","span":{"begin":2196,"end":2198},"obj":"12595898"},{"id":"33082511-28923364-29997634","span":{"begin":2623,"end":2625},"obj":"28923364"},{"id":"33082511-28442746-29997635","span":{"begin":3057,"end":3059},"obj":"28442746"},{"id":"33082511-28361884-29997636","span":{"begin":3466,"end":3468},"obj":"28361884"},{"id":"33082511-29684359-29997637","span":{"begin":3876,"end":3878},"obj":"29684359"},{"id":"33082511-21548792-29997638","span":{"begin":5118,"end":5120},"obj":"21548792"},{"id":"33082511-16723446-29997638","span":{"begin":5118,"end":5120},"obj":"16723446"},{"id":"33082511-27072607-29997638","span":{"begin":5118,"end":5120},"obj":"27072607"},{"id":"33082511-31272712-29997638","span":{"begin":5118,"end":5120},"obj":"31272712"},{"id":"33082511-21228377-29997638","span":{"begin":5118,"end":5120},"obj":"21228377"},{"id":"33082511-23012360-29997638","span":{"begin":5118,"end":5120},"obj":"23012360"},{"id":"33082511-31272712-29997639","span":{"begin":5305,"end":5307},"obj":"31272712"},{"id":"33082511-23645879-29997640","span":{"begin":5308,"end":5311},"obj":"23645879"},{"id":"33082511-25277308-29997640","span":{"begin":5308,"end":5311},"obj":"25277308"},{"id":"33082511-24790856-29997640","span":{"begin":5308,"end":5311},"obj":"24790856"},{"id":"33082511-30419240-29997640","span":{"begin":5308,"end":5311},"obj":"30419240"},{"id":"33082511-21548792-29997641","span":{"begin":5842,"end":5845},"obj":"21548792"},{"id":"33082511-16723446-29997642","span":{"begin":5846,"end":5848},"obj":"16723446"},{"id":"33082511-21548792-29997643","span":{"begin":6216,"end":6218},"obj":"21548792"},{"id":"33082511-25146982-29997644","span":{"begin":6332,"end":6335},"obj":"25146982"},{"id":"33082511-29643724-29997645","span":{"begin":7108,"end":7112},"obj":"29643724"},{"id":"33082511-16723446-29997646","span":{"begin":7263,"end":7265},"obj":"16723446"},{"id":"33082511-24790856-29997647","span":{"begin":7392,"end":7395},"obj":"24790856"},{"id":"33082511-30419240-29997648","span":{"begin":7989,"end":7992},"obj":"30419240"},{"id":"33082511-27072607-29997649","span":{"begin":8099,"end":8102},"obj":"27072607"},{"id":"33082511-28892824-29997650","span":{"begin":8103,"end":8106},"obj":"28892824"},{"id":"33082511-27072607-29997651","span":{"begin":8255,"end":8257},"obj":"27072607"},{"id":"33082511-28892824-29997652","span":{"begin":8422,"end":8425},"obj":"28892824"},{"id":"33082511-30419240-29997653","span":{"begin":8906,"end":8909},"obj":"30419240"}],"text":"FPRs in other mucosal surfaces\n\nFPRs in the oral cavity\nThe oral cavity is the first site at which external substances enter before proceeding into the GI tract and respiratory tract. Many kinds of stimulants, such as food, allergens, and pathogens, enter the oral cavity. The oral cavity is the site with the second largest microbiota after the large intestine4. Because the fundamental role of the mouth is eating, there is constant mastication and physical stimulation. The oral cavity comprises several barrier surfaces, including the lining mucosa, masticatory mucosa, tongue mucosa, and gingival crevice. These surfaces are kept moist by saliva and gingival crevicular fluid80. The immunological feature of the oral cavity is that both mucosal immunity (soluble IgA) and systemic immunity (plasma IgG) protect this site81. Because of the complex immunological conditions, all immune cell types are resident and active in the oral cavity80.\nReports on FPRs in the oral cavity have focused on very narrow aspects: reports on FPR1 have focused on periodontitis, and reports on FPR2 have focused on submandibular gland and saliva production. Periodontitis is a disease caused by gingival infection. Since the 1970s, it has been well known that neutrophils from periodontitis patients have defective FPR1 signaling82,83. In particular, neutrophils from juvenile periodontitis patients showed decreased migratory ability towards fMLP but not C5a83. From these findings, researchers uncovered genetic variations in the FPR1 gene in periodontitis patients84–88. Although the type of periodontitis was different, the genetic variations in FPR1 from periodontitis patients had a common feature; the mutations caused the receptor to malfunction. The FPR1-329T\u003eC and FPR1-378C\u003eG variants cause F110S and C126W amino acid sequence alterations, respectively84. These mutations are associated with decreased migratory ability towards fMLP and defects in G protein coupling85,86. In particular, mutation of amino acid 110 affects the surface expression of FPR186. Other mutations that occur are R190W and N192K, which change the extracellular loop structure of FPR1 and decrease its ligand binding affinity87.\nStudies on the role of FPR2 have focused on the submandibular gland. The submandibular gland is one of the major salivary glands located under the floor of the mouth. Saliva is a watery fluid produced from salivary glands that contains various innate antimicrobial molecules, such as immunoglobulins, lysozyme, and lactoferrin. Decreased saliva production or the absence of saliva increases susceptibility to oral infection80. FPR2 and its ligand RvD1 reduce immune responses in the salivary glands. Fpr2 knockout mice were found to show an enhanced immune response in the salivary gland in an LPS challenge model. These knockout mice exhibited abnormalities such as increased immune cell infiltration in the salivary gland, upregulation of inflammatory cytokines, decreased saliva production, increased apoptosis, and alterations in tight junction proteins89. RvD1 activates FPR2 on the salivary glands and helps to maintain salivary gland integrity and to inhibit apoptosis and TNF-α-mediated inflammation90,91.\nSjogren syndrome (SS) is a chronic autoimmune disease that decreases the function of exocrine glands. As a result, the production of tears and saliva decreases. One study focused on the effect of RvD1 on NOD/ShiLtJ mice, whose phenotype mimics human SS92. RvD1 activates FPR2 expressed on submandibular gland cells, showing a preventive effect on the onset of disease by improving secretory function, decreasing proinflammatory molecule expression, and increasing anti-inflammatory molecule expression and M2 macrophage polarization. Interestingly, old female Fpr2 knockout mice show symptoms similar to those of SS, such as reduced salivary flow and weight loss93. Fpr2 knockout mice have an increased CD20+ B cell population and enhanced autoantibody production in the submandibular glands. This observation implies that FPR2 maintains the functional status of salivary glands by shaping adaptive immunity and regulating the inflammatory response intensity.\n\nFPRs in the eye\nThe eye is an organ of the visual system. The structure of the eye evolved anatomically and immunologically to protect visual function81. Significantly, the exterior surface of the eye is in direct contact with the external environment and encounters an enormous amount of immunogens. The immune response in the eye is strictly regulated to maintain the transparency of the cornea. The ocular mucosal surface includes the cornea and the conjunctiva. Tear film protects these mucosal surfaces, and neural inputs from the cornea and conjunctiva regulate the production of tears. Tears contain various protective substances, such as mucin produced by goblet cells and immunoglobulins produced by plasma cells81.\nFPRs are expressed on various cell types in the ocular region, such as corneal endothelial cells, corneal epithelial cells, conjunctival goblet cells, retinal microglia, retinal pigment cells, and lens epithelial cells94–99. Additionally, various FPR-related ocular pathologies exist, such as retinal degeneration, uveitis, polypoidal choroidal vasculopathy, corneal neovascularization, and ocular allergy97,100–103. However, here, we only discuss the role of FPRs in the cornea and conjunctiva as ocular mucosal surfaces. The cornea is located at the anterior aspect of the eye and passes light to the lens. The immune response in the cornea is unreactive compared to that in the conjunctiva, because inflammation of the cornea can affect its transparency104. FPR2 is expressed on the corneal endothelium and epithelium, and the functional activity of FPR2 in those regions has been indirectly confirmed by effects of the FPR2 antagonist WRW494,95. The cornea is a transplantable tissue, and there are several reports that the ligands of FPR2, including LXA4 and RvD1, can be beneficial during corneal transplantation. LXA4 promotes the proliferation of human corneal endothelial cells, and when added to Optisol-GS, which is the pretransplant storage fluid for corneas, LXA4 reduces corneal endothelial cell damage94. RvD1 reduces allograft mortality during corneal transplantation by regulating DC-mediated inflammatory responses105. Although RvD1 promotes corneal wound healing, it is not clear whether FPR2 mediates the effect of RvD1 in vivo.\nDiabetes is a representative metabolic disease with ocular complications. Diabetic patients show impaired corneal wound healing because of corneal epithelium and nerve defects. RvD1 can improve corneal epithelial regeneration in diabetic mice. RvD1 acts via the following mechanisms: increased expression of proliferation-related molecules (Ki67 and SIRT1), EGFR activation, decreased inflammatory cytokine (TNF-α, IL-1β) production, decreased expression of ROS-generating enzymes (NOX2 and NOX3), and upregulated expression of antioxidant genes (Nrf2, MnSOD, and HO-1). WRW4, the FPR2 antagonist, significantly blocks these various therapeutic effects of RvD1106. Another FPR2 ligand, LL-37, also promotes corneal epithelial cell migration in a PTX- and FPR2-sensitive manner and facilitates corneal wound healing95. Regarding SAA, the expression of Saa1,3 was increased with the expression of Fpr2 in a corneal neovascularization mouse model102. This pattern implies that SAA-FPR2 plays a role in this condition.\nThe conjunctiva is a mucosal tissue composed of three layers: the conjunctival epithelial layer, goblet cell layer, and lamina propria. The lamina propria is the site where immune cells reside and produces immunoregulatory factors. In the conjunctiva, several immune responses, such as antigen processing, cell-mediated immunity, and hypersensitivity, occur104. The conjunctiva exhibits basal expression of FPR1 and FPR2, and FPR1 and FPR2 expression is elevated in the setting of inflammation, such as in allergic conditions103. FPR2 is expressed on conjunctival goblet cells and increases mucin production by recognizing LXA4 and RvD196,107. Intracellular calcium influx is directly related to glycoconjugate secretion, and the LXA4-FPR2 axis can promote mucin secretion via calcium influx96. Various downstream signaling molecules of FPR2 affect calcium influx, which shows that FPR2 signaling and homeostasis of the ocular environment are closely related107.\nOne report addressed AnxA1 and FPRs in the case of ocular allergy. Upon the induction of allergic conjunctivitis in mice, FPR1 and FPR2 expression was increased. Interestingly, AnxA1 knockout mice showed a significant increase in FPR2 expression. AnxA1 is an anti-inflammatory mediator that decreases granulocyte infiltration and proinflammatory cytokine production in allergic conjunctivitis. These protective effects were diminished by treatment with Boc2, a pan-FPR antagonist103."}