Upregulation of RANTES in Psoriatic Keratinocytes: a Possible Pathogenic Mechanism for Psoriasis

Raychaudhuri, Siba P.; Jiang, Wen-Yue; Farber, Eugene M.; Schall, Thomas J.; Ruff, Michael R.; Pert, Candace B.
March 1999
Acta Dermato-Venereologica;03/18/99, Vol. 79 Issue 1, p9
Academic Journal
Intraepidermal collections of neutrophils and lymphocytes are unique features of the inflammatory reaction of psoriasis. Migration of leukocytes from dermis to the epidermis suggests a role for chemotactic agent(s). In recent years, increased levels of chemokines such as IL-8 , GRO-α and MCP-1 have been reported in the keratinocytes of psoriatic tissue. IL-8 and GRO-α belong to a subfamily (C×C) class and MCP-1 is a β chemokine. In this study, we investigated RANTES, which is a ß chemokine (C-C class); RANTES has been found to be associated with various cell-mediated hypersensitive disorders. We obtained eight skin biopsies from chronic psoriatic plaques, and five biopsies each from non-lesional psoriatic skin, lichen planus, eczematous dermatitis and skin from healthy controls. Snap-frozen samples were cut into 7 μm cryosections and stained with 6 mg/ml of monoclonal anti-RANTES mouse IgG (DNAX, Palo Alto, CA). Standard immunohistochemistry techniques were applied. RANTES was detected only in the keratinocytes. The number of keratinocytes in per mm[sup 2] of epidermis stained for RANTES were 116.79±98.42 in psoriatic tissues compared to 32.00±46.05 (p<0.05), 6.39±3.59 (p<0.01), 2.64±1.15 (p<0.01) and 3.53±5.26 (p<0.01), respectively, in the non-lesional, lichen planus, eczematous lesions and normal skin. This is the first study to report that the keratinocytes of psoriatic tissue express high levels of RANTES compared to the controls. IL-8 and related molecules (C×C class) are predominantly chemotactic for neutrophils and MCP-1 is a strong chemotactic factor for monocytes. In contrast, RANTES is chemotactic for memory T cells and activated naive T cells. Increased amounts of RANTES as reported here provide an explanation for migration of the activated T cells to the epidermis of the psoriatic lesions. In addition, RANTES activates T cells. These results suggest that RANTES may have a significant role in the inflammatory process of psoriasis. Our findings further substantiate a regulatory role for keratinocytes in the inflammatory process of psoriasis.


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