TLR3-, TLR7-, and TLR9-mediated production of proinflammatory cytokines and chemokines from murine connective tissue type skin-derived mast cells but not from bone marrow-derived mast cells.
Recent studies have revealed that murine bone marrow-derived cultured mast cells (BMMC), which are phenotypically immature mast cells, express functional TLR2 and TLR4 that recognize distinct pathogen-associated molecules. However, it remains relatively uncertain whether mast cells express other TLR. We recently established a method to obtain large numbers of murine fetal skin-derived cultured mast cells (FSMC); these cells exhibit important features of connective tissue type mast cells. Working with FSMC and BMMC, the TLR mRNA expression profiles were compared between both cell types. Although TLR2 and TLR4 mRNA were detected in both cells at comparable levels, TLR3, TLR7, and TLR9 mRNA were expressed by FSMC at higher levels than by BMMC, suggesting distinct TLR expression profiles among different mast cell populations. With respect to their functional aspects, FSMC, but not BMMC, dose dependently produced proinflammatory cytokines (TNF-alpha and IL-6) and chemokines (RANTES, MIP-1alpha, and MIP-2) in response to poly(I:C), R-848, and CpG oligodeoxynucleotide, which are TLR3, TLR7, and TLR9 activators, respectively. Interestingly, these TLR activators failed to induce degranulation and IL-13 production by both mast cells, although peptidoglycan and LPS (TLR2 and TLR4 activators, respectively) induced IL-13 production by both cells. Mast cells, thus, may have potential to recruit other immune cells to the infected sites by responding to various bacterial and viral components through TLR signaling pathways, presumably being involved in initiating innate immunity and subsequently linking innate and acquired immune responses.
Matsushima
Hironori
H
Department of Dermatology, Faculty of Medicine, University of Yamanashi, 1110 Shimokato, Tamaho, Nakakoma, Yamanashi 409-3898, Japan.
Yamada
Nobuo
N
Matsue
Hiroyuki
H
Shimada
Shinji
S
D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism*; D015550:Cell Degranulation; D002478:Cells, Cultured; D018925:Chemokines / Q000096:biosynthesis*; D016207:Cytokines / Q000096:biosynthesis*; D004268:DNA-Binding Proteins / Q000502:physiology*; D011992:Endosomes / Q000502:physiology; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018793:Interleukin-13 / Q000096:biosynthesis; D008407:Mast Cells / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction; D012867:Skin / Q000166:cytology*; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors
C408982:CPG-oligonucleotide; D018925:Chemokines; D016207:Cytokines; D004268:DNA-Binding Proteins; D018793:Interleukin-13; D008562:Membrane Glycoproteins; D009838:Oligodeoxyribonucleotides; D011956:Receptors, Cell Surface; C477038:Tlr7 protein, mouse; C495370:Tlr9 protein, mouse; D051195:Toll-Like Receptor 2; D051196:Toll-Like Receptor 3; D051197:Toll-Like Receptor 4; D051199:Toll-Like Receptor 7; D051217:Toll-Like Receptor 9; D051193:Toll-Like Receptors