Published online before print May 22, 2003

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(Journal of Leukocyte Biology. 2003;74:295-301.)
© 2003 by Society for Leukocyte Biology

High expression of p21^Waf1 in sarcoid granulomas: a putative role for long-lasting inflammation

Jordi Xaus^*, Núria Besalduch^*, Mònica Comalada^*, Joaquim Marcoval, Ramón Pujol, Juan Mañá and Antonio Celada^*

^* Group of Macrophage Biology, Institute of Biomedical Research of Barcelona-Barcelona Science Park, Spain; and Departments of
Dermatology and
Medicine, Ciutat Sanitària i Universitària de Bellvitge, University of Barcelona, Spain

Correspondence: Antonio Celada, Institute of Biomedical Research of Barcelona, Barcelona Science Park, Josep Samitier 1-5, E-08028 Barcelona, Spain. E-mail: acelada{at}ub.edu

In sarcoid granulomas, apoptotic events are reduced, which explains their characteristic long-lasting inflammation. We have described that interferon- (IFN-) 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- and the cdk inhibitors p21^Waf1 and p27^Kip1 were analyzed. IFN- 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- 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.

Key Words: apoptosis • macrophages • cdk inhibitors • p27^Kip1 • fibronectin

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