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. 1990 Dec 1;172(6):1749–1756. doi: 10.1084/jem.172.6.1749

Stimulation of fibroblast chemotaxis by human recombinant tumor necrosis factor alpha (TNF-alpha) and a synthetic TNF-alpha 31-68 peptide

PMCID: PMC2188741  PMID: 2258704

Abstract

Macrophages are a major source of fibrogenic factors that promote healing of injured tissue. The recruitment of fibroblasts to sites of tissue injury is a prerequisite for optimal repair of tissue damage. In the present study, human recombinant tumor necrosis factor alpha (hrTNF- alpha), a major macrophage-derived cytokine, was demonstrated to be a potent fibroblast chemoattractant, inducing migration at picomolar concentrations. Anti-hrTNF-alpha monoclonal antibody neutralized most of the fibroblast chemotactic activity generated during short-term culture of human peripheral blood monocytes stimulated with bacterial lipopolysaccharide, suggesting that TNF-alpha is a major monocyte- derived fibroblast chemoattractant. The portion of the human TNF-alpha molecule responsible for its chemotactic stimulation of fibroblasts appears to reside in residues 31-68. This region is highly conserved between TNF-alpha and lymphotoxin. This peptide is not only itself chemotactic but is also able to block the chemotactic response of fibroblasts to hrTNF-alpha and vice versa, suggesting that they each mediate fibroblast migration through similar mechanisms. These data further underscore the potential importance of TNF-alpha in modulating a variety of fibroblast functions, including chemotaxis and synthesis of collagen, glycosaminoglycans, interleukin 1 alpha (IL-1 alpha) and - beta, human histocompatibility leukocyte antigen A and B antigens, collagenase, prostaglandin E2, and IL-6.

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Selected References

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