Interleukin-4 Induces Senescence in Human Renal Carcinoma Cell Lines through STAT6 and p38 MAPK
- Authors
- Kim, Hag Dong; Yu, Su-Jin; Kim, Hee Suk; Kim, Yong-Jin; Choe, Jeong Min; Park, Yun Gyu; Kim, Joon; Sohn, Jeongwon
- Issue Date
- 4-10월-2013
- Publisher
- AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
- Keywords
- Interleukin; p38 MAPK; Renal Physiology; Senescence; STAT Transcription Factor; IL-4; Renal Cell Carcinoma; STAT6; p21WAF1; CIP1
- Citation
- JOURNAL OF BIOLOGICAL CHEMISTRY, v.288, no.40, pp.28743 - 28754
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF BIOLOGICAL CHEMISTRY
- Volume
- 288
- Number
- 40
- Start Page
- 28743
- End Page
- 28754
- URI
- https://scholar.korea.ac.kr/handle/2021.sw.korea/101893
- DOI
- 10.1074/jbc.M113.499053
- ISSN
- 0021-9258
- Abstract
- Interleukin (IL)-4, originally identified as a lymphocyte growth factor, can directly inhibit growth of certain tumor cell types. We reported previously that IL-4 induced cell cycle arrest in G(1) phase through an increase in p21(WAF1/CIP1) expression in human renal cell carcinoma (RCC) cell lines. In the present study, we investigated the underlying mechanism of IL-4-induced growth inhibition. In four of six human RCC cell lines, including Caki-1, A498, SNU482, and SNU228, IL-4 induced cellular senescence as demonstrated by enlarged and flattened morphology, increased granularity, and senescence-associated--galactosidase (SA--gal) staining. Signal tranducer and activator of transcription 6 (STAT6) and p38 MAPK were found to mediate IL-4-induced growth inhibition and cellular senescence. Both of these molecules were activated by 10 min after IL-4 treatment, and inhibition of their activity or expression prevented growth suppression and cellular senescence induced by IL-4. Inhibiting or silencing either STAT6 or p38 MAPK alone partially reduced the effect of IL-4, whereas inhibiting or silencing both molecules exerted an additive effect and almost completely abrogated the effect of IL-4. Thus STAT6 and p38 MAPK appeared to independently mediate IL-4-induced growth inhibition and cellular senescence. The p21(WAF1/CIP1) up-regulation that accompanied growth inhibition and cellular senescence by IL-4 was also attenuated additively when p38 MAPK and STAT6 were silenced. Taken together, these results show that IL-4 induces cellular senescence through independent signaling pathways involving STAT6 and p38 MAPK in some human RCC cell lines.
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Collections - College of Medicine > Department of Medical Science > 1. Journal Articles
- Graduate School > Department of Life Sciences > 1. Journal Articles
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