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Hypoxia modulates cyclin and cytokine expression and inhibits peripheral mononuclear cell proliferation
Author(s) -
Naldini Antonella,
Carraro Fabio
Publication year - 1999
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/(sici)1097-4652(199912)181:3<448::aid-jcp8>3.0.co;2-f
Subject(s) - peripheral blood mononuclear cell , hypoxia (environmental) , biology , cyclin , cell cycle , phytohaemagglutinin , cyclin b1 , lymphocyte , immunology , microbiology and biotechnology , apoptosis , cancer research , chemistry , biochemistry , cyclin dependent kinase 1 , in vitro , organic chemistry , oxygen
Previously, we found that hypoxia can deeply affect the production of cytokines in human peripheral mononuclear cells (PBMC). Here, we demonstrated that the cycle progression of hypoxic PBMC, cultured in the presence or not of a specific T cell activator such as phytohaemagglutinin (PHA), was delayed when compared with aerobic cultures. This delay was accompanied by a decrease of the expression of specific cyclins associated to cell cycle progression phases. Ribonuclease Protection Assay (RPA) studies reveal a decrease in the expression of cyclin A and B in PHA‐stimulated PBMC kept for 40 hr under hypoxic condition (2% O 2 ), when compared with aerobic cultures (20% O 2 ). In concomitance, a decrease of cyclin D2 expression was present after 16 hr of hypoxic treatment. However, the decrease was transient and disappeared after 40 hr of hypoxic treatment. Furthermore, cyclin C expression was not affected by hypoxia. Hypoxia‐induced cyclin modulation was accompanied by an increased synthesis of interleukin (IL)‐2 and IL‐4, analyzed by ELISA. By evaluating these results, it appears that hypoxia induces a growth suppressive state in mitogen‐activated PBMC by inhibiting the synthesis of mitotic cyclins A and B. However hypoxic PBMC maintain their viability and capability of producing stimulatory cytokines, after mitogen treatment. This should be important in local hypoxia, usually associated with necrotic areas, in inflammation, and infections, where T lymphocyte capability of producing stimulatory cytokines is desirable. J. Cell. Physiol. 181:448–454, 1999. © 1999 Wiley‐Liss, Inc.