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06.01.2021 | Laboratory Investigation

Role of oncostatin M in the pathogenesis of vernal keratoconjunctivitis: focus on tissue remodeling

verfasst von: Keitaro Mashimo, Ayumi Usui-Ouchi, Yousuke Ito, Rei Wakasa-Arai, Norihiko Yokoi, Satoshi Kawasaki, Akira Murakami, Akira Matsuda, Nobuyuki Ebihara

Erschienen in: Japanese Journal of Ophthalmology | Ausgabe 1/2021

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Abstract

Purpose

Vernal keratoconjunctivitis (VKC) is a severe and recurrent allergic conjunctivitis, the mechanism of which is not well understood. In this study, we investigated the role of oncostatin M (OSM) in the pathogenesis of VKC, with a focus on tissue remodeling.

Study design

Clinical and experimental.

Patients and methods

The OSM concentrations in tear fluid samples obtained from VKC patients and healthy controls were measured using ELISA, and the expression of OSM mRNA and protein in giant papillae resected from VKC patients was investigated using RT-PCR and immunohistochemistry, respectively. In cultured human conjunctival epithelial cells (HconEpiCs), expression of OSM receptor β (OSMRβ) was detected using immunocytochemical and FACS analyses. Finally, we investigated whether recombinant OSM activated STAT1 and STAT3 to induce the expression of various genes related to tissue remodeling in HconEpiCs, by using Western blot analysis, microarray analysis, and RT-PCR.

Results

The OSM concentration was higher in the tear fluid of VKC patients than in that of the healthy controls, and strong expression of OSM mRNA was found in the giant papillae. We also detected T cells expressing OSM in the giant papillae. In addition, HconEpiCs showed surface expression of OSMRβ. Recombinant human OSM strongly activated both STAT1 and STAT3 in HconEpiCs and induced various tissue remodeling-related genes, including MMP-1, MMP-3, IL-24, IL-20, serpinB3, S100A7, tenascin C, and SOCS3.

Conclusion

Our results suggest that OSM is one of the key molecules involved in remodeling of giant papillae in VKC.

Tanaka M, Miyajima A. Oncostatin M: a multifunctional cytokine. Rev Physiol Biochem Pharmacol. 2003;149:39–52.PubMedCrossRef

Jones SA, Jenkins BJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol. 2018;18:773–89.PubMedCrossRef

Boniface K, Diveu C, Morel F, Pedretti N, Froger J, Ravon E, et al. Oncostatin M secreted by skin infiltrating T lymphocytes is a potent keratinocyte activator involved in skin inflammation. J Immunol. 2007;178:4615–22.PubMedCrossRef

Fritz DK, Kerr C, Fattouh R, Llop-Guevara A, Khan WI, Jordana M, et al. A mouse model of airway disease: oncostatin M-induced pulmonary eosinophilia, goblet cell hyperplasia, and airway hyperresponsiveness are STAT6 dependent, and interstitial pulmonary fibrosis is STAT6 independent. J Immunol. 2011;186:1107–18.PubMedCrossRef

Nagahama KY, Togo S, Holz O, Magnussen H, Liu X, Seyama K, et al. Oncostatin M modulates fibroblast function via signal transducers and activators of transcription proteins-3. Am J Respir Cell Mol Biol. 2013;49:582–91.PubMedCrossRef

Kang HJ, Kang JS, Lee SH, Hwang SJ, Chae SW, Woo JS, et al. Upregulation of oncostatin M in allergic rhinitis. Laryngoscope. 2005;115:2213–6.PubMedCrossRef

Mozaffarian A, Brewer AW, Trueblood ES, Luzina IG, Todd NW, Atamas SP, et al. Mechanisms of oncostatin M-induced pulmonary inflammation and fibrosis. J Immunol. 2008;181:7243–53.PubMedCrossRef

Johnson RB. Use of NSAIDs in long-distance runners: a risk factor for sudden death? South Med J. 1989;82:95.PubMedCrossRef

Scaffidi AK, Mutsaers SE, Moodley YP, McAnulty RJ, Laurent GJ, Thompson PJ, et al. Oncostatin M stimulates proliferation, induces collagen production and inhibits apoptosis of human lung fibroblasts. Br J Pharmacol. 2002;136:793–801.PubMedPubMedCentralCrossRef

10.

Duncan MR, Hasan A, Berman B. Oncostatin M stimulates collagen and glycosaminoglycan production by cultured normal dermal fibroblasts: insensitivity of sclerodermal and keloidal fibroblasts. J Invest Dermatol. 1995;104:128–33.PubMedCrossRef

11.

Bamber B, Reife RA, Haugen HS, Clegg CH. Oncostatin M stimulates excessive extracellular matrix accumulation in a transgenic mouse model of connective tissue disease. J Mol Med (Berl). 1998;76:61–9.CrossRef

12.

Wong S, Botelho FM, Rodrigues RM, Richards CD. Oncostatin M overexpression induces matrix deposition, STAT3 activation, and SMAD1 Dysregulation in lungs of fibrosis-resistant BALB/c mice. Lab Invest. 2014;94:1003–16.PubMedCrossRef

13.

Sarkozi R, Hauser C, Noppert SJ, Kronbichler A, Pirklbauer M, Haller VM, et al. Oncostatin M is a novel inhibitor of TGF-beta1-induced matricellular protein expression. Am J Physiol Renal Physiol. 2011;301:F1014–25.PubMedCrossRef

14.

Abe H, Takeda N, Isagawa T, Semba H, Nishimura S, Morioka MS, et al. Macrophage hypoxia signaling regulates cardiac fibrosis via Oncostatin M. Nat Commun. 2019;10:2824.PubMedPubMedCentralCrossRef

15.

Huguier V, Giot JP, Simonneau M, Levillain P, Charreau S, Garcia M, et al. Oncostatin M exerts a protective effect against excessive scarring by counteracting the inductive effect of TGFbeta1 on fibrosis markers. Sci Rep. 2019;9:2113.PubMedPubMedCentralCrossRef

16.

Iwamoto S, Asada Y, Ebihara N, Hori K, Okayama Y, Kashiwakura J, et al. Interaction between conjunctival epithelial cells and mast cells induces CCL2 expression and piecemeal degranulation in mast cells. Invest Ophthalmol Vis Sci. 2013;54:2465–73.PubMedCrossRef

17.

Tanioka H, Kawasaki S, Yamasaki K, Ang LP, Koizumi N, Nakamura T, et al. Establishment of a cultivated human conjunctival epithelium as an alternative tissue source for autologous corneal epithelial transplantation. Invest Ophthalmol Vis Sci. 2006;47:3820–7.PubMedCrossRef

18.

Ang LP, Tanioka H, Kawasaki S, Ang LP, Yamasaki K, Do TP, et al. Cultivated human conjunctival epithelial transplantation for total limbal stem cell deficiency. Invest Ophthalmol Vis Sci. 2010;51:758–64.PubMedCrossRef

19.

Kinoshita S, Kawasaki S, Kitazawa K, Shinomiya K. Establishment of a human conjunctival epithelial cell line lacking the functional TACSTD2 gene (an American Ophthalmological Society thesis). Trans Am Ophthalmol Soc. 2012;110:166–77.PubMedPubMedCentral

20.

Matsuda A, Ebihara N, Yokoi N, Kawasaki S, Tanioka H, Inatomi T, et al. Functional role of thymic stromal lymphopoietin in chronic allergic keratoconjunctivitis. Invest Ophthalmol Vis Sci. 2010;51:151–5.PubMedCrossRef

21.

Pothoven KL, Norton JE, Suh LA, Carter RG, Harris KE, Biyasheva A, et al. Neutrophils are a major source of the epithelial barrier disrupting cytokine oncostatin M in patients with mucosal airways disease. J Allergy Clin Immunol. 2017;139:1966–78.PubMedCrossRef

22.

Suda T, Chida K, Todate A, Ide K, Asada K, Nakamura Y, et al. Oncostatin M production by human dendritic cells in response to bacterial products. Cytokine. 2002;17:335–40.PubMedCrossRef

23.

Salamon P, Shoham NG, Puxeddu I, Paitan Y, Levi-Schaffer F, Mekori YA. Human mast cells release oncostatin M on contact with activated T cells: possible biologic relevance. J Allergy Clin Immunol. 2008;121:448–55.PubMedCrossRef

24.

Grenier A, Dehoux M, Boutten A, Arce-Vicioso M, Durand G, Gougerot-Pocidalo MA, et al. Oncostatin M production and regulation by human polymorphonuclear neutrophils. Blood. 1999;93:1413–21.PubMedCrossRef

25.

Uriarte SM, Powell DW, Luerman GC, Merchant ML, Cummins TD, Jog NR, et al. Comparison of proteins expressed on secretory vesicle membranes and plasma membranes of human neutrophils. J Immunol. 2008;180:5575–81.PubMedCrossRef

26.

Young D, Das N, Anowai A, Dufour A. Matrix metalloproteases as influencers of the cells’ social media. Int J Mol Sci. 2019;20:3847.PubMedCentralCrossRef

27.

Ryan RE, Martin B, Mellor L, Jacob RB, Tawara K, McDougal OM, et al. Oncostatin M binds to extracellular matrix in a bioactive conformation: implications for inflammation and metastasis. Cytokine. 2015;72:71–85.PubMedPubMedCentralCrossRef

28.

Leonardi A, Brun P, Abatangelo G, Plebani M, Secchi AG. Tear levels and activity of matrix metalloproteinase (MMP)-1 and MMP-9 in vernal keratoconjunctivitis. Invest Ophthalmol Vis Sci. 2003;44:3052–8.PubMedCrossRef

29.

Turato C, Pontisso P. SERPINB3 (serpin peptidase inhibitor, clade B (ovalbumin), member 3). Atlas Genet Cytogenet Oncol Haematol. 2015;19:202–9.PubMedPubMedCentral

30.

Reithofer M, Jahn-Schmid B. Allergens with protease activity from house dust mites. Int J Mol Sci. 2017;18:1368.PubMedCentralCrossRef

31.

Pothoven KL, Norton JE, Hulse KE, Suh LA, Carter RG, Rocci E, et al. Oncostatin M promotes mucosal epithelial barrier dysfunction, and its expression is increased in patients with eosinophilic mucosal disease. J Allergy Clin Immunol. 2015;136(737–46):e4.

32.

Pothoven KL, Schleimer RP. The barrier hypothesis and Oncostatin M: restoration of epithelial barrier function as a novel therapeutic strategy for the treatment of type 2 inflammatory disease. Tissue Barriers. 2017;5:e1341367.PubMedPubMedCentralCrossRef

33.

Rutz S, Wang X, Ouyang W. The IL-20 subfamily of cytokines: from host defence to tissue homeostasis. Nat Rev Immunol. 2014;14:783–95.PubMedCrossRef

34.

Tohyama M, Hanakawa Y, Shirakata Y, Dai X, Yang L, Hirakawa S, et al. IL-17 and IL-22 mediate IL-20 subfamily cytokine production in cultured keratinocytes via increased IL-22 receptor expression. Eur J Immunol. 2009;39:2779–88.PubMedCrossRef

35.

Madsen P, Rasmussen HH, Leffers H, Honore B, Dejgaard K, Olsen E, et al. Molecular cloning, occurrence, and expression of a novel partially secreted protein “psoriasin” that is highly up-regulated in psoriatic skin. J Invest Dermatol. 1991;97:701–12.PubMedCrossRef

36.

Hoffmann HJ, Olsen E, Etzerodt M, Madsen P, Thogersen HC, Kruse T, et al. Psoriasin binds calcium and is upregulated by calcium to levels that resemble those observed in normal skin. J Invest Dermatol. 1994;103:370–5.PubMedCrossRef

37.

Alowami S, Qing G, Emberley E, Snell L, Watson PH. Psoriasin (S100A7) expression is altered during skin tumorigenesis. BMC Dermatol. 2003;3:1.PubMedPubMedCentralCrossRef

38.

Ostergaard M, Wolf H, Orntoft TF, Celis JE. Psoriasin (S100A7): a putative urinary marker for the follow-up of patients with bladder squamous cell carcinomas. Electrophoresis. 1999;20:349–54.PubMedCrossRef

39.

Vegfors J, Ekman AK, Stoll SW, Bivik Eding C, Enerback C. Psoriasin (S100A7) promotes stress-induced angiogenesis. Br J Dermatol. 2016;175:1263–73.PubMedCrossRef

40.

Giblin SP, Midwood KS. Tenascin-C: form versus function. Cell Adh Migr. 2015;9:48–82.PubMedCrossRef

41.

Bhattacharyya S, Wang W, Morales-Nebreda L, Feng G, Wu M, Zhou X, et al. Tenascin-C drives persistence of organ fibrosis. Nat Commun. 2016;7:11703.PubMedPubMedCentralCrossRef

42.

Ohtomo K, Ebihara N, Matsuda A, Tokura T, Funaki T, Murakami A. Role of TGF-beta in tissue eosinophilia associated with vernal keratoconjunctivitis. Exp Eye Res. 2010;91:748–54.PubMedCrossRef

Titel: Role of oncostatin M in the pathogenesis of vernal keratoconjunctivitis: focus on tissue remodeling
verfasst von: Keitaro Mashimo
Ayumi Usui-Ouchi
Yousuke Ito
Rei Wakasa-Arai
Norihiko Yokoi
Satoshi Kawasaki
Akira Murakami
Akira Matsuda
Nobuyuki Ebihara
Publikationsdatum: 06.01.2021
Verlag: Springer Japan
Erschienen in: Japanese Journal of Ophthalmology / Ausgabe 1/2021
Print ISSN: 0021-5155
Elektronische ISSN: 1613-2246
DOI: https://doi.org/10.1007/s10384-020-00791-8

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Role of oncostatin M in the pathogenesis of vernal keratoconjunctivitis: focus on tissue remodeling

Abstract

Purpose

Study design

Patients and methods

Results

Conclusion

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Springer Medizin

Abstract

Purpose

Study design

Patients and methods

Results

Conclusion

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