title: Desert dust induces TLR signaling to trigger Th2-dominant lung allergic inflammation via a MyD88-dependent signaling pathway.
abstract: Asian sand dust (ASD) is known to exacerbate asthma, although its mechanism is not yet well understood. In this study, when the effects on inflammatory response by LPS present in ASD was investigated by measuring the gene expression of cytokines and chemokines in RAW264.7 cells treated with ASD and/or polymyxin B (PMB), the ASD effects were attenuated by PMB, but not completely. When an in vitro study was performed using bone marrow-derived macrophages (BMDMs) from WT, TLR2(-/-), TLR4(-/-), and MyD88(-/-) BALB/c mice and BMDMs from WT, TLR2(-/-), TLR4(-/-), TLR2/4(-/-), TLR7/9(-/-), and MyD88(-/-) C57BL/6J mice, cytokine (IL-6, IL-12) production in BMDMs was higher in ASD-stimulated TLR2(-/-) cells than in TLR4(-/-) cells, whereas it was lower or undetectable in TLR2/4(-/-) and MyD88(-/-) cells. These results suggest that ASD causes cytokine production predominantly in a TLR4/MyD88-dependent pathway. When WT and TLRs 2(-/-), 4(-/-), and MyD88(-/-) BALB/c mice were intratracheally challenged with OVA and/or ASD, ASD caused exacerbation of lung eosinophilia along with Th2 cytokine and eosinophil-relevant chemokine production. Serum OVA-specific IgE and IgG1 similar to WT was observed in TLRs 2(-/-), 4(-/-) mice, but not in MyD88(-/-) mice. The Th2 responses in TLR2(-/-) mice were attenuated remarkably by PMB. These results indicate that ASD exacerbates lung eosinophilia in a MyD88-dependent pathway. TLRs 2 and 4 signaling may be important in the increase in lung eosinophilia. Also, the TLR4 ligand LPS and TLR2 ligand like β-glucan may be strong candidates for exacerbation of lung eosinophilia.
authors.affiliation: Environment and Non-communicable Disease Research Center, School of Public Health, China Medical University, Shenyang 110122, China. Electronic address: hemiao@mail.cmu.edu.cn.
authors.forename: Miao
authors.initials: M
authors.lastname: He
authors.affiliation: Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201, Japan. Electronic address: ichinose@oita-nhs.ac.jp.
authors.forename: Takamichi
authors.initials: T
authors.lastname: Ichinose
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Fukuoka 807-8555, Japan.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Song
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Fukuoka 807-8555, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Department of Environmental Health, National Institute of Public Health, Saitama 351-0197, Japan.
authors.forename: Kanae
authors.initials: K
authors.lastname: Bekki
authors.affiliation: Department of Immunology and Parasitology, School of Medicine, University of Occupational and Environmental Health, Fukuoka 807-8555, Japan.
authors.forename: Keiichi
authors.initials: K
authors.lastname: Arashidani
authors.affiliation: Department of Health Sciences, Oita University of Nursing and Health Sciences, Oita 870-1201, Japan.
authors.forename: Seiichi
authors.initials: S
authors.lastname: Yoshida
authors.affiliation: Environmental Chemistry Division, National Institute for Environmental Studies, Ibaraki 305-8506, Japan.
authors.forename: Masataka
authors.initials: M
authors.lastname: Nishikawa
authors.affiliation: Environmental Health Division, Department of Environmental Engineering, Graduate School of Engineering, Kyoto University, Kyoto 615-8530, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Takano
authors.affiliation: Department of Environmental Toxicology, University of California, Davis, CA 95616, USA.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Shibamoto
authors.affiliation: Environment and Non-communicable Disease Research Center, School of Public Health, China Medical University, Shenyang 110122, China.
authors.forename: Guifan
authors.initials: G
authors.lastname: Sun
mesh_terms: D000818:Animals; D002460:Cell Line; D004391:Dust; D018836:Inflammation Mediators / Q000276:immunology / Q000378:metabolism*; D008168:Lung / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053594:Myeloid Differentiation Factor 88 / Q000276:immunology / Q000378:metabolism*; D011657:Pulmonary Eosinophilia / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D018418:Th2 Cells / Q000378:metabolism*; D051193:Toll-Like Receptors / Q000172:deficiency* / Q000276:immunology
chemical_list: D004391:Dust; D018836:Inflammation Mediators; C507780:Myd88 protein, mouse; D053594:Myeloid Differentiation Factor 88; D051193:Toll-Like Receptors
keywords: Asthma; Desert dust; MyD88 deficiency; TLR deficiency