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High expression of p21 Waf1 in sarcoid granulomas: a putative role for long‐lasting inflammation
Author(s) -
Xaus Jordi,
Besalduch Núria,
Comalada Mònica,
Marcoval Joaquim,
Pujol Ramón,
Mañá Juan,
Celada Antonio
Publication year - 2003
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.1202628
Subject(s) - inflammation , sarcoidosis , granuloma , biology , apoptosis , immunohistochemistry , interferon gamma , gene expression , immunology , reverse transcriptase , pathology , gene , cancer research , microbiology and biotechnology , polymerase chain reaction , immune system , medicine , biochemistry
In sarcoid granulomas, apoptotic events are reduced, which explains their characteristic long‐lasting inflammation. We have described that interferon‐γ (IFN‐γ) inhibits apoptosis in macrophages through the expression of p21 Waf1 . Here, we explore the molecular mechanisms involved in the inhibition of apoptosis in sarcoid granulomas. We analyzed skin biopsies from 19 sarcoidosis patients and 16 controls. Total RNA was subjected to semiquantitative reverse transcriptase‐polymerase chain reaction analysis. There was no difference found in the expression of proapoptotic (Bax and Bcl‐X s ) or antiapoptotic (Bcl‐2 and Bcl‐X L ) genes nor in the expression of the tumor suppressor gene p53. Furthermore, the expression of IFN‐γ and the cdk inhibitors p21 Waf1 and p27 Kip1 were analyzed. IFN‐γ was detected in 37% of the sarcoidosis patients, and controls were negative ( P <0.02). In addition, a higher proportion of patients expressing p21 Waf1 (58%) versus controls (12%) was found ( P <0.005). There was a significant correlation between the expression of IFN‐γ and p21 Waf1 (r=0.69) and between p21 Waf1 and fibronectin (r=0.65). Finally, using immunohistochemistry, high p21 Waf1 reactivity was observed inside the granuloma. We conclude that the high levels of p21 Waf1 in sarcoidosis may explain the absence of apoptosis in the granuloma and the persistence of inflammation.