Eceptor expression in keloid and normal fibroblastsChatanya S. Nirodi, PhDa,b, Radika Devalaraja, PhDa,b, Lillian B. Nanney, PhDa,b,c, Saundrett Arrindell, MDd, Shirley Russell, PhDe, Joel Trupin, PhDe, and Ann Richmond, PhDa,b aDepartment of Veterans Affairs, Vanderbilt University College of Medicine, Nashville, Tennessee.bDepartment cDepartment dDepartment eDepartmentof Cell Biology, Vanderbilt University College of Medicine, Nashville, Tennessee. of Plastic Surgery, Vanderbilt University College of Medicine, Nashville, Tennessee. of Medicine, Meharry Health-related College, Nashville, Tennessee. of Microbiology, Meharry Health-related College, Nashville, Tennessee.AbstractKeloids are benign collagenous tumors that happen during dermal wound healing in genetically predisposed folks. The lesions are characterized by over-proliferation of fibroblasts, some leukocyte infiltration, and prolonged high rates of collagen synthesis. To identify no matter whether leukocyte chemoattractants or chemokines are participating in this illness approach, immunohistochemical staining for the CXC chemokine, MGSA/GRO, and its receptor, CXCR2, was performed on PPARβ/δ Antagonist Synonyms tissue from keloids, hypertrophic scars and standard skin. Immunoreactive MGSA/GRO was not observed in hypertrophic scars or normal dermis, but was present in some myofibroblasts and lymphocytes in nodular regions with the keloid samples. This staining NF-κB Activator Compound positively correlated with all the degree of inflammatory infiltrate within the lesions. Keloids, but not hypertrophic scars or normal dermis, also exhibited intensive immunoreactivity for the CXCR2 receptor in endothelial cells and inflammatory infiltrates with occasional staining of myofibroblasts. In contrast, cultured fibroblasts from either keloids or regular skin did not express detectable amounts of mRNA for MGSA/GRO or CXCR2, although interleukin-1 strongly induced MGSA/ GRO mRNA in both cell types. Interleukin-1 induction of MGSA/GRO was inhibited by glucocorticoid in regular and keloid fibroblasts, plus the effect was additional pronounced in keloid fibroblasts. This occasion was not correlated with inhibition of nuclear activation of NF-B, AP-1 or Sp1, and may possibly therefore be mediated by a further mechanism including decreased mRNA stability or transcriptional repression through the glucocorticoid response element in the MGSA/GRO promoter. Data from in vitro wounding experiments with cultured regular and keloid fibroblasts indicate that there had been no important variations in MGSA/GRO or CXCR2 receptor levels in between regular and keloid fibroblasts. We also show that cultured keloid fibroblasts exhibit a delayed wound healing response. We postulate that the inflammatory element is significant in improvement of keloid lesions and chemotactic cytokines might participate in this process. Keloids are benign collagenous tumors that form within the reticular layer with the dermis in the course of a prolonged wound healing process in persons with a genetic predisposition.1,2 Keloids occur predominantly in Black and Asian populations. The altered tissue repair mechanism appearsCopyright 2000 by the Wound Healing Society. Reprint requests: Ann Richmond, PhD, Department of Cell Biology, MCN T2212, Vanderbilt University College of Medicine, Nashville, TN 37232. Fax: (615) 343-4539; [email protected] et al.Pageto be restricted to dermal wound healing, mainly because other development or connective tissue abnormalities usually are not regularly reported in keloid sufferers. The disorder may perhaps be genetically heterogeneous, w.