Hypoxic Stress Induced TREM-1 and Inflammatory Chemokines in Human Peripheral Blood Mononuclear Cells

Abstract

Hypoxia is a condition of low pO 2 , 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.

Chemokines in High Altitude Pulmonary Edema

“…Indeed hypoxia exposure whether, in vitro or in vivo, is associated with rise in inflammatory markers. However, in the previous studies, as also quoted in the article by the authors, the duration of hypoxia exposure varied from 16 to 72 h [2][3][4][5] On the contrary, in the present study duration of simulated hypoxia of 4500 m was only 30 min. It remains obscure that those changes seen in the chemokines are actually the result of hypoxia induced inflammation or otherwise.…”

Cobalt Alloy Implant Debris Induces Inflammation and Bone Loss Primarily through Danger Signaling, Not TLR4 Activation: Implications for DAMP-ening Implant Related Inflammation

“…It has also been demonstrated that that Nickel and Cobalt ions can induce IL-8 production via human TLR4 activation [ 17 ; 55 ]. However, it has also been reported that hypoxia can result in up-regulation of both TLR4 expression and IL-8 production and thus, whether this TLR4 induced IL-8 is a primary or secondary effect of Cobalt is not known [ 56 ; 57 ]. Therefore, it is possible that previous investigations of observed cobalt induced IL-8 may have been due to Cobalt toxicity responses eliciting a hypoxia state and increased endogenous alarmins/DAMPs (i.e.…”

The Contact Allergen NiSO4 Triggers a Distinct Molecular Response in Primary Human Dendritic Cells Compared to Bacterial LPS

“…Elevated HIF1α activity eventually resulted in elevated IL-8 expression. TREM1 protein expression and IL-8 secretion were both previously reported to be increased under hypoxic conditions ( 68 ). We could show that NiSO 4 -treated MoDCs also induced TREM1 signaling as well as IL-8 secretion.…”