15-Lipoxygenase-2 expression in human macrophages induces chemokine secretion and T cell migration.

• BACKGROUND: We determined previously that hypoxia results in increased 15-lipoxygenase type 2 (15-LOX-2) expression and CXCL8 secretion in macrophages. This study sought to determine whether 15-LOX-2 expression links directly with the secretion of inflammatory molecules in macrophages and also investigated its subsequent effects on T cell migration. METHODS: Adenovirus-mediated gene delivery caused overexpression of 15-LOX-2 in human macrophages. We used cytometric bead array to measure chemokine secretion, and assessed T cell migration by counting cells in chemotaxis chambers. Expression of chemokine receptors was determined by FACS analysis. Using siRNA, we reduced 15-LOX-2 expression in human macrophages. We used scrambled siRNA as control. RESULTS: Macrophages that overexpress 15-LOX-2 showed increased secretion of chemokine CXCL10 after 24h incubation. In addition, preconditioned medium from 15-LOX-2-overexpressing cells increased T cell migration and surface expression of CXCR3, the CXCL10 receptor. Knockdown of 15-LOX-2 expression decreased CXCL10 secretion from hypoxic macrophages and also reduced T cell migration. CONCLUSION: In macrophages, overexpression of 15-LOX-2 results in increased secretion of CXCL10 and CCL2. Products released in response to increased 15-LOX-2 activation lead to increased expression of CD69, the T cell activation marker as well as increased T cell migration. Therefore, increased expression of 15-LOX-2 induced by hypoxia may participate in T cell recruitment in diseases such as atherosclerosis.

Nyckelord

Adenoviridae

genetics

Antigens

CD

genetics

Antigens

Differentiation

T-Lymphocyte

genetics

Arachidonate 15-Lipoxygenase

genetics

metabolism

secretion

Atherosclerosis

immunology

metabolism

physiopathology

CD4-Positive T-Lymphocytes

cytology

Cell Communication

immunology

Cell Movement

immunology

Cells

Cultured

Chemokine CXCL10

metabolism

secretion

Gene Expression

immunology

Humans

Interleukin-8

metabolism

secretion

Macrophages

cytology

enzymology

secretion

RNA

Small Interfering

Transgenes

Vasculitis

immunology

metabolism

physiopathology

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