PMID- 26244295 OWN - NLM STAT- MEDLINE DCOM- 20151027 LR - 20221207 IS - 1552-5783 (Electronic) IS - 0146-0404 (Linking) VI - 56 IP - 9 DP - 2015 Aug TI - Roles of Epithelial Cell-Derived Type 2-Initiating Cytokines in Experimental Allergic Conjunctivitis. PG - 5194-202 LID - 10.1167/iovs.15-16563 [doi] AB - PURPOSE: To clarify the possible involvement of the type 2-initiating cytokines interleukin (IL)-25, IL-33, and thymic stromal lymphopoietin (TSLP) in the pathophysiology of allergic conjunctivitis, we evaluated ragweed (RW)-induced experimental allergic conjunctivitis (EAC) models by using IL-25 knockout (KO), IL-33 KO, and TSLP receptor (TSLPR) KO mice. METHODS: Interleukin-25 KO, IL-33 KO, TSLPR KO, and BALB/c wild-type mice were sensitized twice with RW in alum and then challenged with RW in eye drops. Clinical scores and eosinophil infiltration were evaluated. Expression levels of serum immunoglobulin E (IgE) and cytokines in the conjunctival tissues were quantified and immunohistochemical analysis was carried out. RESULTS: Significant reductions in clinical scores and numbers of infiltrating eosinophils were observed in the RW-EAC model using IL-33 KO mice. There were no significant differences in clinical scores and numbers of infiltrating eosinophils among IL-25KO, TSLPR KO, and wild-type mice. Serum IgE concentration was upregulated after RW challenges, and there were no differences among the mouse genotypes. Expression levels of of il4, il5, il13, and ccl5 mRNA were diminished in the conjunctivae of the RW-EAC model using IL-33 KO mice compared to those in wild-type mice. Interleukin-33 expression was upregulated as early as 1 hour after RW eye-drop challenge. The number of infiltrating basophils in the conjunctivae of the RW-EAC model using IL-33 KO mice was diminished compared to that in wild-type mice. CONCLUSIONS: Among the type 2-initiating cytokines, IL-33 may play a major role in conjunctival inflammation in an RW-EAC model. FAU - Asada, Yosuke AU - Asada Y AD - Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan 2Frontier Research Initiative, Institute of Medical Science, University of Tokyo, Tokyo, Japan. FAU - Nakae, Susumu AU - Nakae S AD - Frontier Research Initiative, Institute of Medical Science, University of Tokyo, Tokyo, Japan. FAU - Ishida, Waka AU - Ishida W AD - Department of Ophthalmology, Kochi University School of Medicine, Nangoku, Japan. FAU - Hori, Kanji AU - Hori K AD - Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. FAU - Sugita, Jobu AU - Sugita J AD - Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. FAU - Sudo, Katsuko AU - Sudo K AD - Animal Research Center, Tokyo Medical University, Tokyo, Japan. FAU - Fukuda, Ken AU - Fukuda K AD - Department of Ophthalmology, Kochi University School of Medicine, Nangoku, Japan. FAU - Fukushima, Atsuki AU - Fukushima A AD - Department of Ophthalmology, Kochi University School of Medicine, Nangoku, Japan. FAU - Suto, Hajime AU - Suto H AD - Department of Dermatology, Juntendo University School of Medicine, Tokyo, Japan 6Atopy Research Center, Juntendo University School of Medicine, Tokyo, Japan. FAU - Murakami, Akira AU - Murakami A AD - Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. FAU - Saito, Hirohisa AU - Saito H AD - Department of Allergy and Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. FAU - Ebihara, Nobuyuki AU - Ebihara N AD - Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. FAU - Matsuda, Akira AU - Matsuda A AD - Laboratory of Ocular Atopic Diseases Department of Ophthalmology, Juntendo University School of Medicine, Tokyo, Japan. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Invest Ophthalmol Vis Sci JT - Investigative ophthalmology & visual science JID - 7703701 RN - 0 (Cytokines) RN - 0 (Il33 protein, mouse) RN - 0 (Interleukin-17) RN - 0 (Interleukin-33) RN - 0 (Interleukins) RN - 0 (Mydgf protein, mouse) RN - 37341-29-0 (Immunoglobulin E) RN - 63231-63-0 (RNA) RN - GT0IL38SP4 (Thymic Stromal Lymphopoietin) RN - 0 (TSLP protein, mouse) SB - IM MH - Animals MH - Cells, Cultured MH - Conjunctiva/immunology/*metabolism/pathology MH - Conjunctivitis, Allergic/*genetics/immunology/pathology MH - Cytokines/biosynthesis/*genetics MH - Disease Models, Animal MH - *Gene Expression Regulation MH - Immunoglobulin E/biosynthesis/genetics MH - Immunohistochemistry MH - Interleukin-17/biosynthesis/*genetics MH - Interleukin-33 MH - Interleukins/biosynthesis/*genetics MH - Mice MH - Mice, Inbred BALB C MH - Mice, Knockout MH - RNA/genetics MH - Real-Time Polymerase Chain Reaction MH - Thymic Stromal Lymphopoietin EDAT- 2015/08/06 06:00 MHDA- 2015/10/28 06:00 CRDT- 2015/08/06 06:00 PHST- 2015/08/06 06:00 [entrez] PHST- 2015/08/06 06:00 [pubmed] PHST- 2015/10/28 06:00 [medline] AID - 2424447 [pii] AID - 10.1167/iovs.15-16563 [doi] PST - ppublish SO - Invest Ophthalmol Vis Sci. 2015 Aug;56(9):5194-202. doi: 10.1167/iovs.15-16563.