TY - JOUR
T1 - Interferon-γ differentially regulates TGF-β1 and TGF-β2 expression in human retinal pigment epithelial cells through JAK-STAT pathway
AU - Nagineni, Chandrasekharam N.
AU - Cherukuri, Karthik S.
AU - Kutty, Veena
AU - Detrick, Barbara
AU - Hooks, John J.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2007/1
Y1 - 2007/1
N2 - Retinal pigment epithelium (RPE) and transforming growth factor-β (TGF-β) have been shown to be involved in various retinal diseases. We have studied the role of inflammatory cytokines on the expression and secretion of TGF-β in human RPE cells (HRPE). Confluent cultures of HRPE derived from donor eyes were used. RT-PCR analyses showed that TNF-α and IL-1β increased the mRNA levels of both TGF-β1 and TGF-β2. IFN-γ enhanced constitutively expressed, as well as, TNF-α-and IL-β-induced TGF-β1 mRNA levels but decreased TGF-β2 mRNA. The effects of these cytokines on TGF-β1 and TGF-β2 secretion correlated with the mRNA levels. TGF-β1 was always produced as the latent form while 21-31% of TGF-β2 was in the active form. IFN-γ reduced the production of active form of TGF-β2 to 4-9%. TGF-β3 secretion was not detectable under any of the conditions. The Real-Time PCR analysis of TGF-β mRNAs confirmed the observed results. The TGF-β1 and TGF-β2 secretion was induced by TGF-β2 and TGF-β1, respectively. Under these conditions, the contrasting effects of IFN-γ on TGF-β1 and TGF-β2 secretion were also observed. JAK inhibitor selectively inhibited IFN-γ induced TGF-β1 secretion and mRNA levels while reversing the inhibitory effects of IFN-γ on TGF-β2. Analyses of transcription factor activity strongly indicated the role of STAT-1 but not NFκB, C-Myc, C-Jun, SP-1, MEF-2. Our data demonstrate that IFN-γ differentially regulates constitutively expressed, as well as, cytokine-induced TGF-β1 and TGF-β2 mRNA levels and secretion of TGF-βs by HRPE.
AB - Retinal pigment epithelium (RPE) and transforming growth factor-β (TGF-β) have been shown to be involved in various retinal diseases. We have studied the role of inflammatory cytokines on the expression and secretion of TGF-β in human RPE cells (HRPE). Confluent cultures of HRPE derived from donor eyes were used. RT-PCR analyses showed that TNF-α and IL-1β increased the mRNA levels of both TGF-β1 and TGF-β2. IFN-γ enhanced constitutively expressed, as well as, TNF-α-and IL-β-induced TGF-β1 mRNA levels but decreased TGF-β2 mRNA. The effects of these cytokines on TGF-β1 and TGF-β2 secretion correlated with the mRNA levels. TGF-β1 was always produced as the latent form while 21-31% of TGF-β2 was in the active form. IFN-γ reduced the production of active form of TGF-β2 to 4-9%. TGF-β3 secretion was not detectable under any of the conditions. The Real-Time PCR analysis of TGF-β mRNAs confirmed the observed results. The TGF-β1 and TGF-β2 secretion was induced by TGF-β2 and TGF-β1, respectively. Under these conditions, the contrasting effects of IFN-γ on TGF-β1 and TGF-β2 secretion were also observed. JAK inhibitor selectively inhibited IFN-γ induced TGF-β1 secretion and mRNA levels while reversing the inhibitory effects of IFN-γ on TGF-β2. Analyses of transcription factor activity strongly indicated the role of STAT-1 but not NFκB, C-Myc, C-Jun, SP-1, MEF-2. Our data demonstrate that IFN-γ differentially regulates constitutively expressed, as well as, cytokine-induced TGF-β1 and TGF-β2 mRNA levels and secretion of TGF-βs by HRPE.
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U2 - 10.1002/jcp.20839
DO - 10.1002/jcp.20839
M3 - Article
C2 - 17013806
AN - SCOPUS:33845404109
SN - 0021-9541
VL - 210
SP - 192
EP - 200
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 1
ER -