Down modulation of IFN-γ signaling in alveolar macrophages isolated from smokers

Division of Pulmonary and Critical Care Medicine, Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, Kansas, USA.
Toxicology and Applied Pharmacology (Impact Factor: 3.63). 04/2009; 237(1):22-8. DOI: 10.1016/j.taap.2009.02.021
Source: PubMed

ABSTRACT The master cytokine, IFN-gamma possesses a wide spectrum of biological effects and is crucial for development of the highly activated macrophage phenotype characteristically found during inflammation. However, no data exists regarding the potential influence of cigarette smoke on the status of the expression of the cell surface receptor for IFN-gamma (IFN-gammaR) on alveolar macrophages (AM) of smokers. Here in, we report reduction in the expression of the IFN-gammaR alpha-chain on AM of cigarette smokers, when compared with non-smokers. Ensuing from the loss of receptor expression on the AM of smokers there was a decrease in IFN-gamma-mediated cell signaling. This included a decrease in the phosphorylation of signal transducer and activator of transcription (STAT)-1 and induction of interferon regulatory factor (IRF)-1. Further, diminished activation/induction of transcription factors did not appear to result from induction of known members of the 'suppressors of cytokine signaling (SOCS)' family. Decreased IFN-gamma signal transduction in AM from smokers may have an important implication regarding the use of therapeutic IFN-gamma in the lungs of patients that develop respiratory disorders as a result of tobacco use.

Download full-text


Available from: Heath E Latham, Jul 20, 2015
  • Source
    • "The degeneration of normal mucociliary processes in the COPD airways due to accumulated lifetime cigarette-smoke exposure contributes to the colonization of NTHI in the lower respiratory tract. It is now well accepted that cigarettesmoke alters the immune response in the airways and even impacts adversely on systemic immunity (Domagala-Kulawik, 2008; Mehta et al., 2008; Dhillon et al., 2009; Stämpfli and Anderson, 2009). This alteration negatively influences the innate immune response to bacterial infection, which further dysregulates inflammatory cascades in the respiratory mucosa. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Non-typeable Haemophilus influenzae (NTHI) colonizes the lower respiratory tract of patients with chronic obstructive pulmonary disease and also causes exacerbations of the disease. The 16-kDa lipoprotein P6 has been widely studied as a potential vaccine antigen due to its highly conserved expression amongst NTHI strains. Although P6 is known to induce potent inflammatory responses, its role in the pathogenesis of NTHI infection in vivo has not been examined. Additionally, the presence of an amino-terminal lipid motif on P6 serves to activate host Toll-like receptor 2 (TLR2) signaling. The role of host TLR2 and NTHI expression of the lipoprotein P6 on the induction of airway inflammation and generation of adaptive immune responses following chronic NTHI stimulation was evaluated with TLR2-deficient mice and a P6-deficient NTHI strain. Absence of either host TLR2 or bacterial P6 resulted in diminished levels of immune cell infiltration within lungs of mice exposed to NTHI. Pro-inflammatory cytokine secretion was also reduced in lungs that did not express TLR2 or were exposed to NTHI devoid of P6. Induction of specific antibodies to P6 was severely limited in TLR2-deficient mice. Although mice exposed to the P6-deficient NTHI strain were capable of generating antibodies to other surface antigens of NTHI, these levels were lower compared to those observed in mice exposed to P6-expressing NTHI. Therefore, cognate interaction between host TLR2 and bacterial P6 serves to enhance lung inflammation and elicit robust adaptive immune responses during NTHI exposure. Strategies to limit NTHI inflammation while simultaneously promoting robust immune responses may benefit from targeting the TLR2:P6 signaling axis.
    Frontiers in Immunology 04/2011; 2:10. DOI:10.3389/fimmu.2011.00010
  • [Show abstract] [Hide abstract]
    ABSTRACT: Summary form only given. In order to bridge the gap between traditional value-added activities chain and knowledge development, this paper attempts to introduce a new concept of “knowledge transformation chain” by examining the existing forms of knowledge, the changes of interaction pattern between these forms and the linkages of value-added activities and the transformation of knowledge in its existing forms. The theoretical investigation of this paper reveals technology exists in three forms instead of traditional two forms, i.e. hardware and software. The medium form technology, which is mainly in the form of design, written documents and other medium outputs of materialising human concepts, is expanding. Secondly, the pattern of knowledge transformation has shown a dramatic change due to the burgeoning of the medium form technology. A multi-stage and multi-path knowledge transformation process has replaced the traditional static and one-step process. Thirdly, applying the concept of knowledge transformation chain to physical value-added activities model, a firm's value creation process can be seen as the fabrication of a value net by weaving the three forms of knowledge into a functional activities chain in a firm. On the one hand, knowledge transformation process affects a firm's value-added activity selection. On the other hand, a firm's value-added activity affects its knowledge transformation chain interact with those of other firms
    Management of Engineering and Technology, 1999. Technology and Innovation Management. PICMET '99. Portland International Conference on; 02/1999
  • [Show abstract] [Hide abstract]
    ABSTRACT: The aims of the present study were to investigate the immunomodulatory effect of a Sophora subprosrate polysaccharide (SSP1) on splenic lymphocyte proliferation, production of cytokines and antioxidant capacities in dexamethasone-induced immunosuppressed mice. The results showed that SSP1 stimulated proliferation and IFN-gamma secretion of murine splenic lymphocytes at concentrations of 50, 100, 200 or 400 mg/L in vitro. SSP1 increased the levels of interleukin-6 and tumor necrosis factor-alpha in immunosuppressed mice induced by subcutaneous injection of dexamethasone at 1.25 mg/kg. Administration of SSP1 by intraperitoneal injection significantly raised spleen index, glutathione level, glutathione peroxidase activity and lysozyme activity in the immunosuppressed mice. This suggests that SSP1 may play an important role in regulating immunological functions in mice.
    International journal of biological macromolecules 11/2009; 46(1):79-84. DOI:10.1016/j.ijbiomac.2009.10.016 · 3.10 Impact Factor
Show more