Hypoxic Stress Induced TREM-1 and Inflammatory Chemokines in Human Peripheral Blood Mononuclear Cells.
Hypoxia is a condition of low pO2, which creates a unique microenvironment affecting cell phenotype and subsequent immune response generation. Little is known about the impact of hypoxia on the phenotypic expression of NK cell, TREM-1, TLR-4 and inflammatory chemokines. In the present study we have determined the frequency of peripheral blood populations of CD16/CD56 (NK Cells) expressing cells, presence of activation marker CD354 (TREM-1), Toll like receptor (CD 284) on the cell surface and chemokines IL-8 and RANTES in the cellular supernatant of normoxia and hypoxia exposed cells by flow cytometry. GRP-78 expression was determined by reverse transcriptase polymerase chain reaction. The blood was collected from healthy individuals and exposed to normoxic and hypoxic (0.5 %) environment for 24 h. The percentage of NK cells (CD 16/56) was marginally up regulated while TLR-4 expression was diminished in hypoxia exposed cells as compare to the normoxic cells. TREM-1 expression was significantly up-regulated (p < 0.05) in hypoxia as compared to the normoxic control. In addition when monocytic cell line THP-1 was exposed to 0.5 % hypoxia for 24 h, TLR4 expression was significantly decreased in hypoxic cells as compared to normoxic cells. Furthermore, GRP-78 mRNA expression was also upregulated by hypoxia or LPS exposure. These events are paralleled by strengthening up-regulation of the chemokines IL-8 and RANTES an otherwise necessary event for the chemotaxis of the neutrophils and macrophages to the inflammatory site. In conclusion, this study provides a novel insight into the mechanism linking low oxygen tension to the regulation of immune and inflammatory responses, leading to new perspectives of the role of hypoxia in programming immune cell functions.
Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 India.
K P
KP
Mishra
Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 India.
Sonal
S
Jain
Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 India.
Lilly
L
Ganju
Immunomodulation Laboratory, Defence Institute of Physiology and Allied Sciences, Lucknow Road, Timarpur, Delhi, 110054 India.
S B
SB
Singh
Chemokine; GRP-78; Hypoxia; IL-8; Inflammation; RANTES