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M Zhang, EF Foxman, S Hurst, T Muchamuel, DF Shen, EF Wawrousek, CC Chan, I Gery; Differential Expression of Cytokines, Chemokines and Chemokine Receptors in Th1- vs Th2-mediated Ocular Inflammation . Invest. Ophthalmol. Vis. Sci. 2002;43(13):884.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: To identify inflammatory mediators involved in T-cell mediated ocular inflammation. Methods: Ocular inflammation was induced in mice by two procedures: (i) adoptive transfer of polarized Th1 or Th2 lymphocytes sensitized against hen egg lysozyme (HEL) into recipient mice expressing HEL in their eyes, or (ii) induction of EAU by immunization with IRBP. Development of inflammation was assessed by histological examination. Expression of mRNA transcripts of 34 cytokines, 26 chemokines and 14 chemokine receptors was quantified in whole eye extracts by real-time RT-PCR. RPE cells and infiltrating leukocytes were collected from inflamed eyes by laser capture microdissection and their chemokine transcript expression was determined by RT-PCR. Results: (1) Three patterns of upregulation of cytokines, chemokines and chemokine receptor transcripts were seen in recipients of adoptively transferred Th cells: preferential expression in Th1 recipients, or in Th2 recipients, or similar expression in both recipient groups. (2) Upregulated transcripts in Th1 recipients included: IL-1α, IL-1ß, IL-1RA, IL-6, IFN-γ, TNF-α, MIG, IP-10, MCP-1, MCP-3, RANTES, MIP1α, MIP1ß, CCR-1, CCR-5, CCR-2, CXCR-3 and CCR-7, while in Th2 cell recipients the elevated transcripts were: IL-4, IL-5, IL-9, IL-13, eotaxin, TARC and CCR-3. Three transcripts were similarly upregulated in both Th1 and Th2 recipients: C-10, MIP-1γ and MDC. (3) In EAU, the inflammatory mediator expression pattern closely paralleled that seen in Th1-induced disease. (4) Both RPE and infiltrating leukocytes expressed chemokine transcripts in distinct but overlapping patterns in inflamed eyes. (5) Interestingly, transcripts of multiple cytokines, chemokines, and chemokine receptors were constitutively expressed in high levels in intact mouse eyes. Seven of these molecules have not been previously associated with the eye. Conclusions: This study identifies for the first time a large battery of molecules involved in the induction of immune-mediated ocular inflammation. Remarkable differences were noted between the groups of molecules upregulated in Th1- or in Th2-induced inflammation, while close similarity was found between the transcript profiles of Th1-induced disease and EAU.
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