Molecular and Cellular Biochemistry

, Volume 303, Issue 1–2, pp 259–262 | Cite as

Hypoxia and antioxidants enhance soluble ICAM-1 release from cardiac fibroblasts

  • S. Sapna
  • K. ShivakumarEmail author


Intercellular adhesion molecule-1 plays a key role in mediating inflammatory and immune responses. There is also increasing appreciation of the role of its soluble form, sICAM-1, in regulating inflammation. This study evaluated the effects of hypoxia and N-acetyl-L-cysteine on sICAM-1 production by adult rat cardiac fibroblasts. By ELISA, hypoxia was found to cause a 61% increase in sICAM-1 in cardiac fibroblast culture supernates. However, RT-PCR did not reveal a concomitant increase in cell surface ICAM-1 transcript levels, suggesting that the increase in sICAM-1 may involve post-transcriptional and/or post-translational mechanisms. Using pharmacological inhibitors, it was observed that p42/44 MAPK and PKC mediate the stimulatory effect of hypoxia on sICAM-1 production. Remarkably, N-acetyl-L-cysteine caused a 3-fold increase in sICAM-1 by p42/44 MAPK-, p38 MAPK- and PKC-independent mechanisms. Pyrrolidine dithiocarbamate, another potent antioxidant, also augmented sICAM-1. The findings presented in this communication underscore the link between redox status and sICAM-1 release from cardiac fibroblasts. Further, because hypoxia is a major component of myocardial ischemia and is pro-inflammatory, and both N-acetylcysteine and pyrrolidine dithiocarbamate are clinically used antioxidants, the observations may have clinical significance.


Cardiac fibroblasts sICAM-1 Hypoxia N-acetyl-L-cysteine Pyrrolidine dithiocarbamate p42/44 MAPK Protein kinase C 



This work was supported by a research grant to K Shivakumar from the Department of Biotechnology, Government of India. S Sapna acknowledges the Research Fellowship from the Department of Biotechnology. The authors thank Dr Sankara Sarma of SCTIMST for statistical analysis of the data.


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© Springer Science+Business Media, LLC 2007

Authors and Affiliations

  1. 1.Division of Cellular and Molecular CardiologySree Chitra Tirunal Institute for Medical Sciences and TechnologyTrivandrumIndia

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