Chemokine and chemokine receptor expression in keloid and normal fibroblasts

Keloids are benign collagenous tumors that occur during dermal wound healin g in genetically predisposed individuals. The lesions are characterized by over-proliferation of fibroblasts, some leukocyte infiltration, and prolong ed high rates of collagen synthesis. To determine whether leukocyte chemoat tractants or chemokines are participating in this disease process, immunohi stochemical staining for the CXC chemokine, MGSA/GRO alpha, and its recepto r, CXCR2, was performed on tissue from keloids, hypertrophic scars and norm al skin. Immunoreactive MGSA/GRO alpha was not observed in hypertrophic sca rs or normal dermis, but was present in some myofibroblasts and lymphocytes in nodular areas of the keloid samples. This staining positively correlate d with the degree of inflammatory infiltrate in the lesions. Keloids, but n ot hypertrophic scars or normal dermis, also exhibited intensive immunoreac tivity for the CXCR2 receptor in endothelial cells and inflammatory infiltr ates with occasional staining of myofibroblasts. In contrast, cultured fibr oblasts from either keloids or normal skin did not express detectable amoun ts of mRNA for MGSA/GRO or CXCR2, although interleukin-1 strongly induced M GSA/GRO mRNA in both cell types. Interleukin-1 induction of MGSA/GRO was in hibited by glucocorticoid in normal and keloid fibroblasts, and the effect was more pronounced in keloid fibroblasts. This event was not correlated wi th inhibition of nuclear activation of NF-kappaB, AP-1 or Sp1, and might th erefore be mediated by another mechanism such as decreased mRNA stability o r transcriptional repression through the glucocorticoid response element in the MGSA/GRO promoter. Data from in vitro wounding experiments with cultur ed normal and keloid fibroblasts indicate that there were no significant di fferences in MGSA/GRO or CXCR2 receptor levels between normal and keloid fi broblasts. We also show that cultured keloid fibroblasts exhibit a delayed wound healing response. We postulate that the inflammatory component is imp ortant in development of keloid lesions and chemotactic cytokines may parti cipate in this process.