PMID- 17068485 OWN - NLM STAT- MEDLINE DCOM- 20070212 LR - 20221109 IS - 1523-1747 (Electronic) IS - 0022-202X (Linking) VI - 127 IP - 2 DP - 2007 Feb TI - Human keratinocytes express functional Toll-like receptor 3, 4, 5, and 9. PG - 331-41 AB - Keratinocytes are continuously in contact with external stimuli and have the capacity to produce several soluble mediators. Pathogen-associated molecular patterns (PAMPs) are recognized, among others, by Toll-like receptors (TLRs). The functional responses of keratinocytes to different PAMPs have not yet been fully established. Here we show that keratinocytes constitutively express TLR1, 2, 3, 4, 5, 6, 9, and 10 mRNA, but not TLR7 and 8. Stimulation of keratinocytes with TLR3, 4, 5, and 9 ligands resulted in differential immune-associated responses. Tumor necrosis factor-alpha, CXC chemokine ligand 8 (CXCL8), CCL2, and C chemokine ligand 20 (CCL20) release was enhanced in response to all PAMPs tested, in a time- and dose-dependent manner. Only TLR9 ligand CpG-oligodeoxynucleotides (ODNs) and TLR3 ligand poly-I:C could additionally induce type I IFNs. CCL27 production was selectively induced by poly-I:C and flagellin, whereas CXCL9 and CXCL10 were exclusively induced by CpG-ODNs and/or poly-I:C. Upregulation of ICAM-1, HLA-DR, HLA-ABC, FasR, and CD40 was mainly observed in response to poly-I:C, flagellin, and lipopolysaccharide. Furthermore, PAMP triggering resulted in the phosphorylation of phosphorylated-IkappaB alpha and in the nucleus translocation of NF-kappaB p65. Altogether, these findings stress an unexpectedly multifaceted role of keratinocytes in innate immunity as evident by their differential, TLR-mediated responses to PAMPs associated with different classes of pathogens. FAU - Lebre, Maria C AU - Lebre MC AD - Department of Cell Biology and Histology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. FAU - van der Aar, Angelic M G AU - van der Aar AM FAU - van Baarsen, Lisa AU - van Baarsen L FAU - van Capel, Toni M M AU - van Capel TM FAU - Schuitemaker, Joost H N AU - Schuitemaker JH FAU - Kapsenberg, Martien L AU - Kapsenberg ML FAU - de Jong, Esther C AU - de Jong EC LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20061026 PL - United States TA - J Invest Dermatol JT - The Journal of investigative dermatology JID - 0426720 RN - 0 (CXCL10 protein, human) RN - 0 (CXCL9 protein, human) RN - 0 (Chemokine CXCL10) RN - 0 (Chemokine CXCL9) RN - 0 (Chemokines) RN - 0 (Chemokines, CXC) RN - 0 (Cytokines) RN - 0 (I-kappa B Proteins) RN - 0 (Ligands) RN - 0 (Lipopolysaccharides) RN - 0 (Oligonucleotides) RN - 0 (Protein Isoforms) RN - 0 (RNA, Messenger) RN - 0 (Toll-Like Receptor 3) RN - 0 (Toll-Like Receptor 4) RN - 0 (Toll-Like Receptor 5) RN - 0 (Toll-Like Receptor 9) RN - 0 (Toll-Like Receptors) RN - 0 (Transcription Factor RelA) RN - 12777-81-0 (Flagellin) RN - O84C90HH2L (Poly I-C) SB - IM CIN - J Invest Dermatol. 2007 Feb;127(2):262-3. PMID: 17228303 MH - Biological Transport MH - Cell Nucleus/metabolism MH - Cells, Cultured MH - Chemokine CXCL10 MH - Chemokine CXCL9 MH - Chemokines/metabolism MH - Chemokines, CXC/metabolism MH - CpG Islands MH - Cytokines/metabolism MH - Flagellin/pharmacology MH - Humans MH - I-kappa B Proteins/metabolism MH - Keratinocytes/*metabolism MH - Ligands MH - Lipopolysaccharides/pharmacology MH - Oligonucleotides/genetics/pharmacology MH - Phosphorylation MH - Poly I-C/pharmacology MH - Protein Isoforms/metabolism MH - RNA, Messenger/metabolism MH - Tissue Distribution MH - Toll-Like Receptor 3/genetics/*metabolism MH - Toll-Like Receptor 4/genetics/*metabolism MH - Toll-Like Receptor 5/genetics/*metabolism MH - Toll-Like Receptor 9/genetics/*metabolism MH - Toll-Like Receptors/genetics/metabolism MH - Transcription Factor RelA/metabolism EDAT- 2006/10/28 09:00 MHDA- 2007/02/13 09:00 CRDT- 2006/10/28 09:00 PHST- 2006/10/28 09:00 [pubmed] PHST- 2007/02/13 09:00 [medline] PHST- 2006/10/28 09:00 [entrez] AID - S0022-202X(15)33246-2 [pii] AID - 10.1038/sj.jid.5700530 [doi] PST - ppublish SO - J Invest Dermatol. 2007 Feb;127(2):331-41. doi: 10.1038/sj.jid.5700530. Epub 2006 Oct 26.