Human keratinocytes express functional CD14 and toll-like receptor 4.
CD14 and the toll-like receptor 4 have been known to play an important role in lipopolysaccharide-induced cellular responses in bacterial infections. Although CD14 and toll-like receptor 4 expression has been demonstrated in a number of myeloid cells, much less is known about the expression and function of these lipopolysaccharide receptors on nonleukocytes. In this study, we demonstrate that human keratinocytes are capable of expressing functional CD14 and toll-like receptor 4. Keratinocytes were found to constitutively express CD14 and toll-like receptor 4 mRNA that was augmented by exposure to lipopolysaccharide. Cell surface expression of keratinocyte CD14 and toll-like receptor 4 was detected by flow cytometry. Lipopolysaccharide binding to keratinocyte CD14 and toll-like receptor 4 resulted in a rapid intracellular Ca2+ response, nuclear factor-kappaB nuclear translocation, and the secretion of proinflammatory cytokines and chemokines. These results have important implications for our understanding of cutaneous innate immunity to bacterial infections of the skin.
Department of Dermatology, Northwestern University The Feinberg School of Medicine, Chicago, Illinois 60611, USA.
Peter I
PI
Song
Young-Min
YM
Park
Tonya
T
Abraham
Brad
B
Harten
Adam
A
Zivony
Natalia
N
Neparidze
Cheryl A
CA
Armstrong
John C
JC
Ansel
D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis; D016207:Cytokines / Q000096:biosynthesis; D029721:Drosophila Proteins; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000737:chemistry*; D018950:Lipopolysaccharide Receptors / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D016328:NF-kappa B / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000032:analysis* / Q000235:genetics / Q000502:physiology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors
D018925:Chemokines; D016207:Cytokines; D029721:Drosophila Proteins; D018950:Lipopolysaccharide Receptors; D008070:Lipopolysaccharides; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D002118:Calcium