Cutting edge: the immunostimulatory activity of the lung surfactant protein-A involves Toll-like receptor 4.
The collectin surfactant protein-A (SP-A) is involved in the innate host defense and the regulation of inflammatory processes in the lung. In this work we investigated the molecular mechanisms related to the immunostimulatory activity of SP-A using macrophages from C3H/HeJ mice, which carry an inactivating mutation in the Toll-like receptor (TLR)4 gene, and TLR4-transfected Chinese hamster ovary cells. We demonstrate that SP-A-induced activation of the NF-kappaB signaling pathway and up-regulation of cytokine synthesis such as TNF-alpha and IL-10 are critically dependent on the TLR4 functional complex. These findings support the concept that TLR4 is a pattern recognition receptor that signals in response to both foreign pathogens and endogenous host mediators.
Guillot
Loïc
L
Unité de Défense Innée et Inflammation, Institut Pasteur, Institut National de la Santé et de la Recherche Médicale, Unité 485, Paris, France.
Balloy
Viviane
V
McCormack
Francis X
FX
Golenbock
Douglas T
DT
Chignard
Michel
M
Si-Tahar
Mustapha
M
D000276:Adjuvants, Immunologic / Q000502:physiology*; D000818:Animals; D001854:Bone Marrow Cells / Q000276:immunology / Q000378:metabolism; D016466:CHO Cells; D006224:Cricetinae; D016207:Cytokines / Q000378:metabolism; D029721:Drosophila Proteins; D005260:Female; D006801:Humans; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008809:Mice, Inbred C3H; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology; D011510:Proteolipids / Q000502:physiology*; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants / Q000502:physiology*; D011956:Receptors, Cell Surface / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D020298:U937 Cells
D000276:Adjuvants, Immunologic; D016207:Cytokines; D029721:Drosophila Proteins; D008562:Membrane Glycoproteins; D016328:NF-kappa B; D011510:Proteolipids; D037662:Pulmonary Surfactant-Associated Protein A; D037661:Pulmonary Surfactant-Associated Proteins; D011663:Pulmonary Surfactants; D011956:Receptors, Cell Surface; C495345:TLR4 protein, human; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors