Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-γ-stimulated rat astrocytes

Eun Jung Park, Kyung A. Ji, Sae B. Jeon, Woo Hyuck Choi, Inn O. Han, Hye J. You, Jae-Hong Kim, Ilo Jou, Eun H. Joe

Research output: Contribution to journalArticle

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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 languageEnglish
Pages (from-to)5697-5703
Number of pages7
JournalJournal of Immunology
Volume173
Issue number9
Publication statusPublished - 2004 Nov 1

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Astrocytes
Astrocytoma
Phosphorylation
GTP Phosphohydrolases
Intercellular Adhesion Molecule-1
Genes

ASJC Scopus subject areas

  • Immunology

Cite this

Park, E. J., Ji, K. A., Jeon, S. B., Choi, W. H., Han, I. O., You, H. J., ... Joe, E. H. (2004). Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-γ-stimulated rat astrocytes. Journal of Immunology, 173(9), 5697-5703.

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 journalArticle

Park, EJ, Ji, KA, Jeon, SB, Choi, WH, Han, IO, You, HJ, Kim, J-H, Jou, I & Joe, EH 2004, 'Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-γ-stimulated rat astrocytes', Journal of Immunology, vol. 173, no. 9, pp. 5697-5703.
Park EJ, Ji KA, Jeon SB, Choi WH, Han IO, You HJ et al. Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-γ-stimulated rat astrocytes. Journal of Immunology. 2004 Nov 1;173(9):5697-5703.
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. / Rac1 contributes to maximal activation of STAT1 and STAT3 in IFN-γ-stimulated rat astrocytes. In: Journal of Immunology. 2004 ; Vol. 173, No. 9. pp. 5697-5703.
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AU - Han, Inn O.

AU - You, Hye J.

AU - Kim, Jae-Hong

AU - Jou, Ilo

AU - Joe, Eun H.

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