Activation of keratinocyte protein kinase C zeta in psoriasis plaques.
PKCzeta (protein kinase C-zeta), a member of protein kinase C family, plays an important role in cell proliferation, differentiation, and apoptosis. It acts as a downstream molecule for TNF-alpha (tumor necrosis factor) signal transduction and also regulates the expression of CD1d, an HLA-class I-like molecule. The interaction of CD1d with natural killer T (NKT) cells has been shown to be important in their Th1 cytokine production in psoriasis. In this study, we examined PKCzeta in psoriasis in order to define its role in the pathogenesis of the disease. We found that T-cell receptor (TCR) V alpha24+ V beta11+ NKT cells and CD1d molecules within psoriatic skin were increased. Moreover, there was an associated increase in PKCzeta mRNA and protein expression with membrane translocation in psoriasis lesions compared to uninvolved skin. Furthermore, cultured keratinocytes exhibited increased PKCzeta activity and membrane translocation upon stimulation by TNF-alpha, a cytokine known to play an important role in the pathogenesis of psoriasis. These results implied that PKCzeta is an important transduction molecule downstream of TNF-alpha signaling and is associated with increased expression of CD1d that may enhance CD1d-NKT cell interactions in psoriasis lesions. This makes PKCzeta a tempting target for possible pharmacological intervention in modifying the downstream effects of TNF-alpha in psoriasis.
Zhao
Yuming
Y
Department of Dermatology, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA.
Fishelevich
Rita
R
Petrali
John P
JP
Zheng
Lida
L
Anatolievna
Malinina Alla
MA
Deng
April
A
Eckert
Richard L
RL
Gaspari
Anthony A
AA
D018949:Antigens, CD1 / Q000378:metabolism; D055610:Antigens, CD1d; D002460:Cell Line; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D007694:Killer Cells, Natural / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D011565:Psoriasis / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism / Q000494:pharmacology; D000099221:Protein Kinase C zeta
D018949:Antigens, CD1; D055610:Antigens, CD1d; D011493:Protein Kinase C; D012333:RNA, Messenger; D011948:Receptors, Antigen, T-Cell; D014409:Tumor Necrosis Factor-alpha; D000099221:Protein Kinase C zeta; C526877:CD1D protein, human