Enhanced chemokine-receptor expression, function, and signaling in healthy African American and scleroderma-patient monocytes are regulated by caveolin-1

Fibrogenesis & Tissue Repair
Rebecca LeeElena Tourkina

Abstract

A major health disparity suffered by African Americans (AA) is a predisposition toward fibrotic diseases of the skin, lung, and other organs. We previously showed that healthy AA and scleroderma (systemic sclerosis (SSc)) patient monocytes share biochemical and functional differences from control Caucasian (C) monocytes that may predispose AA to SSc. The central difference is a decrease in caveolin-1. Low caveolin-1 levels promote monocyte migration, their differentiation into fibrocytes, and fibrocyte recruitment into fibrotic tissues. Here we have greatly expanded our studies on the mechanism of action in fibrosis of caveolin-1 in AA and SSc monocytes. Expression of chemokine receptors (CCR1, CCR2, CCR3) is enhanced in healthy AA monocytes compared to healthy C monocytes and further increased in SSc monocytes. A parallel increase in function occurs assessed by migration toward chemokines MCP-1 and MCP-3. Chemokine-receptor expression and function are inhibited by the caveolin-1 scaffolding domain peptide (CSD) via its action as a surrogate for caveolin-1. Cells bearing chemokine receptors accumulate to high levels in fibrotic lung and skin tissue from SSc patients and from mice treated with bleomycin. This accumulation is alm...Continue Reading

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Jun 20, 2016·Clinical Reviews in Allergy & Immunology·Gleb Slobodin, Doron Rimar
Dec 19, 2017·Frontiers in Immunology·Cecília Jacques Gonçalves de Almeida
May 3, 2019·Npj Regenerative Medicine·Ilja L Kruglikov, Philipp E Scherer
May 28, 2019·Annals of the Rheumatic Diseases·Adi MorMarco Matucci-Cerinic
Apr 20, 2017·Frontiers in Pharmacology·Rebecca LeeElena Tourkina
Jan 24, 2017·Laboratory Investigation; a Journal of Technical Methods and Pathology·Dorea Pleasant-JenkinsDhandapani Kuppuswamy
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Apr 4, 2021·International Journal of Molecular Sciences·Hee Jin ParkSang-Il Lee
Sep 2, 2021·Clinical Reviews in Allergy & Immunology·Alain LescoatDinesh Khanna

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Methods Mentioned

BETA
bronchoalveolar lavage
immunodepletion
electrophoresis
FCS

Software Mentioned

GraphPad
Image J
NIH
Prism

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