Pulmonary surfactant protein A regulates TLR expression and activity in human macrophages.
نویسندگان
چکیده
The pulmonary innate immune system responds to various airborne microbes. Although its specificity is broad and based on the recognition of pathogen-associated molecular patterns, it is uniquely regulated to limit inflammation and thereby prevent damage to the gas-exchanging alveoli. Macrophages, critical cell determinants of this system, recognize microbes through pattern recognition receptors such as TLRs, which typically mediate proinflammatory responses. The lung collectin, surfactant protein A (SP-A), has emerged as an important innate immune determinant that regulates microbe-macrophage interactions in this environment. In this study, we report the basal and SP-A-induced transcriptional and posttranslational regulation of TLR2 and TLR4 expression during the differentiation of primary human monocytes into macrophages. Despite SP-A's ability to up-regulate TLR2 expression on human macrophages, it dampens TLR2 and TLR4 signaling in these cells. SP-A decreases the phosphorylation of IkappaBalpha, a key regulator of NF-kappaB activity, and nuclear translocation of p65 which result in diminished TNF-alpha secretion in response to TLR ligands. SP-A also reduces the phosphorylation of TLR signaling proteins upstream of NF-kappaB, including members of the MAPK family. Finally, we report for the first time that SP-A decreases the phosphorylation of Akt, a major cell regulator of NF-kappaB and potentially MAPKs. These data identify a critical role for SP-A in modulating the lung inflammatory response by regulating macrophage TLR activity.
منابع مشابه
Pulmonary surfactant protein A and surfactant lipids upregulate IRAK-M, a negative regulator of TLR-mediated inflammation in human macrophages.
Alveolar macrophages (AMs) are exposed to frequent challenges from inhaled particulates and microbes and function as a first line of defense with a highly regulated immune response because of their unique biology as prototypic alternatively activated macrophages. Lung collectins, particularly surfactant protein A (SP-A), contribute to this activation state by fine-tuning the macrophage inflamma...
متن کاملSurfactant Protein (SP)-A Suppresses Preterm Delivery and Inflammation via TLR2
Toll like receptors (TLRs) are pattern-recognition molecules that initiate the innate immune response to pathogens. Pulmonary surfactant protein (SP)-A is an endogenously produced ligand for TLR2 and TLR4. SP-A has been proposed as a fetally produced signal for the onset of parturition in the mouse. We examined the effect of interactions between SP-A and the pathogenic TLR agonists lipopolysacc...
متن کاملEffect of A-769662, a direct AMPK activator, on Tlr-4 expression and activity in mice heart tissue
Objective(s): TLR-4 activates a number of inflammatory signaling pathways. Also, AMPK could be involved in anti-inflammatory signaling. The aim of this study was to identify whether stimulation of AMPK could inhibit LPS-induced Tlr-4 gene expression in mice hearts. Materials and methods: Heart AMPK activity and/or Tlr-4 expression was stimulated in different mice groups, using respectively IP i...
متن کاملPulmonary surfactant protein A up-regulates activity of the mannose receptor, a pattern recognition receptor expressed on human macrophages.
Inhaled particulates and microbes are continually cleared by a complex array of lung innate immune determinants, including alveolar macrophages (AMs). AMs are unique cells with an enhanced capacity for phagocytosis that is due, in part, to increased activity of the macrophage mannose receptor (MR), a pattern recognition receptor for various microorganisms. The local factors that "shape" AM func...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Journal of immunology
دوره 180 12 شماره
صفحات -
تاریخ انتشار 2008