Abstract
Rac1 GTPase is implicated as a signaling mediator in various cellular events. In this study, we show that Rac1 contributes to IFN-γ-induced inflammatory responses in rat astrocytes. We revealed that IFN-γ rapidly stimulated activation of Rac1 in C6 astroglioma cells by investigating GST-PAK-PBB-binding ability. We also found that Rac1 deficiency led to attenuation of IFN-γ-responsive transcriptional responses. Compared with levels in control cells, IFN-γ-induced IFN-γ-activated sequence promoter activity was markedly reduced in both C6 astroglioma cells and primary astrocytes expressing RacN17, a well-characterized Rac1-negative mutant. The expression of several IFN-γ-responsive genes, such as MCP-1 and ICAM-1, was also reduced in cells expressing RacN17. Consistent with these observations, IFN-γ-induced phosphorylation of STAT1 and STAT3 was lower in C6 cells expressing RacN17 (referred to as C6-RacN17) than in control cells. However, there was no difference in expression level of IFN-γRα subunit and IFN-γ-induced phosphorylation of JAK1 between C6 control and C6-RacN17 cells. Interestingly, Rac1 appeared to associate with IFN-γRα and augment the interaction of IFN-γR with either STAT1 or STAT3 in response to IFN-γ Taken together, we suggest that Rac1 may serve as an auxiliary mediator of IFN-γ-signaling, at least at the level of STAT activation, thus contributing to maximal activation of IFN-γ-responsive inflammatory signaling in rat astrocytes.
| Original language | English |
|---|---|
| Pages (from-to) | 5697-5703 |
| Number of pages | 7 |
| Journal | Journal of Immunology |
| Volume | 173 |
| Issue number | 9 |
| Publication status | Published - 2004 Nov 1 |
Fingerprint
ASJC Scopus subject areas
- Immunology
Cite this
Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-γ-stimulated rat astrocytes. / Park, Eun Jung; Ji, Kyung A.; Jeon, Sae B.; Choi, Woo Hyuck; Han, Inn O.; You, Hye J.; Kim, Jae-Hong; Jou, Ilo; Joe, Eun H.
In: Journal of Immunology, Vol. 173, No. 9, 01.11.2004, p. 5697-5703.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-γ-stimulated rat astrocytes
AU - Park, Eun Jung
AU - Ji, Kyung A.
AU - Jeon, Sae B.
AU - Choi, Woo Hyuck
AU - Han, Inn O.
AU - You, Hye J.
AU - Kim, Jae-Hong
AU - Jou, Ilo
AU - Joe, Eun H.
PY - 2004/11/1
Y1 - 2004/11/1
N2 - Rac1 GTPase is implicated as a signaling mediator in various cellular events. In this study, we show that Rac1 contributes to IFN-γ-induced inflammatory responses in rat astrocytes. We revealed that IFN-γ rapidly stimulated activation of Rac1 in C6 astroglioma cells by investigating GST-PAK-PBB-binding ability. We also found that Rac1 deficiency led to attenuation of IFN-γ-responsive transcriptional responses. Compared with levels in control cells, IFN-γ-induced IFN-γ-activated sequence promoter activity was markedly reduced in both C6 astroglioma cells and primary astrocytes expressing RacN17, a well-characterized Rac1-negative mutant. The expression of several IFN-γ-responsive genes, such as MCP-1 and ICAM-1, was also reduced in cells expressing RacN17. Consistent with these observations, IFN-γ-induced phosphorylation of STAT1 and STAT3 was lower in C6 cells expressing RacN17 (referred to as C6-RacN17) than in control cells. However, there was no difference in expression level of IFN-γRα subunit and IFN-γ-induced phosphorylation of JAK1 between C6 control and C6-RacN17 cells. Interestingly, Rac1 appeared to associate with IFN-γRα and augment the interaction of IFN-γR with either STAT1 or STAT3 in response to IFN-γ Taken together, we suggest that Rac1 may serve as an auxiliary mediator of IFN-γ-signaling, at least at the level of STAT activation, thus contributing to maximal activation of IFN-γ-responsive inflammatory signaling in rat astrocytes.
AB - Rac1 GTPase is implicated as a signaling mediator in various cellular events. In this study, we show that Rac1 contributes to IFN-γ-induced inflammatory responses in rat astrocytes. We revealed that IFN-γ rapidly stimulated activation of Rac1 in C6 astroglioma cells by investigating GST-PAK-PBB-binding ability. We also found that Rac1 deficiency led to attenuation of IFN-γ-responsive transcriptional responses. Compared with levels in control cells, IFN-γ-induced IFN-γ-activated sequence promoter activity was markedly reduced in both C6 astroglioma cells and primary astrocytes expressing RacN17, a well-characterized Rac1-negative mutant. The expression of several IFN-γ-responsive genes, such as MCP-1 and ICAM-1, was also reduced in cells expressing RacN17. Consistent with these observations, IFN-γ-induced phosphorylation of STAT1 and STAT3 was lower in C6 cells expressing RacN17 (referred to as C6-RacN17) than in control cells. However, there was no difference in expression level of IFN-γRα subunit and IFN-γ-induced phosphorylation of JAK1 between C6 control and C6-RacN17 cells. Interestingly, Rac1 appeared to associate with IFN-γRα and augment the interaction of IFN-γR with either STAT1 or STAT3 in response to IFN-γ Taken together, we suggest that Rac1 may serve as an auxiliary mediator of IFN-γ-signaling, at least at the level of STAT activation, thus contributing to maximal activation of IFN-γ-responsive inflammatory signaling in rat astrocytes.
UR - http://www.scopus.com/inward/record.url?scp=6344272990&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=6344272990&partnerID=8YFLogxK
M3 - Article
C2 - 15494521
AN - SCOPUS:6344272990
VL - 173
SP - 5697
EP - 5703
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 9
ER -