IL-11 expression in retinal and corneal cells is regulated by interferon-gamma.
Interleukin-11 (IL-11) is an anti-apoptotic, anti-inflammatory cytokine with hematopoietic potential. The expression and protective actions of IL-11 have not been explored in the eye. The expression of IL-11 in primary cultures of human retinal pigment epithelial (HRPE) and human corneal fibroblast (HCRF) cells were evaluated in these studies. Constitutive secretion of IL-11 was not observed in either HRPE or HCRF. TNF-alpha+IL-1 induced IL-11 secretion and this production was inhibited by NFkappaB pathway inhibitors. IFN-gamma significantly inhibited TNF-alpha and IL-1 induced IL-11 secretion and inhibitors of JAK-STAT pathway reversed this inhibition. TGF-beta induced IL-11 secretion that was blocked by TGF-beta receptor 1 inhibitor but not by IFN-gamma. RT-PCR analysis confirmed the effects of IL-1, TNF-alpha, IFN-gamma and TGF-beta on IL-11 secretion at mRNA levels. Our results demonstrate that IL-11 is dramatically up regulated in retina and cornea cells and that IFN-gamma is a physiological inhibitor of IL-11 expression.
Nagineni
Chandrasekharam N
CN
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, United States.
Kommineni
Vijay K
VK
William
Abitha
A
Hooks
John J
JJ
Detrick
Barbara
B
D002460:Cell Line; D003315:Cornea / Q000166:cytology / Q000276:immunology*; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism* / Q000494:pharmacology; D007375:Interleukin-1 / Q000378:metabolism / Q000494:pharmacology; D017370:Interleukin-11 / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D053612:Janus Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000276:immunology*; D050791:STAT Transcription Factors / Q000037:antagonists & inhibitors / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology
D007375:Interleukin-1; D017370:Interleukin-11; D016328:NF-kappa B; D050791:STAT Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D053612:Janus Kinases