Activation of the TNF alpha-p55 receptor induces myocyte proliferation and modulates agonist-evoked calcium transients in cultured human tracheal smooth muscle cells.

Evidence suggests that cytokines may modulate smooth muscle cell function in a variety of inflammatory diseases. In the present study, we characterized the specific receptor subtypes that mediate tumor necrosis factor alpha (TNF alpha) effects on myocyte proliferation and on agonist-induced calcium transients in cultured human tracheal smooth muscle cells (TSMC). Pretreatment of human TSMC with TNF alpha potentiated cytosolic calcium [(Ca2+)i] transients evoked by carbachol. In a similar manner, selective TNF alpha-p55 receptor agonists such as htr-9, an activating monoclonal antibody, or a recombinant TNF-p55 (rTNF-p55), which specifically activates the TNF alpha-p55 receptor but not the TNF alpha-p75 receptor, also augmented [Ca2+]i transients evoked by carbachol. In parallel experiments, TNF alpha, rTNF alpha-p55, and htr-9 induced human TSMC proliferation as measured by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Interestingly, activation of the TNF alpha-p75 receptor with a selective agonist, recombinant TNF alpha-p75 (rTNF alpha-p75), or inhibition of the TNF alpha-p75 receptor with utr-1, an inhibitory anti-TNF alpha-p75 receptor antibody, had no effect on TNF alpha-augmented calcium transients or on myocyte growth. To further confirm the receptor specificity of these findings, immunocytochemical studies were performed using receptor-specific antibodies. These studies demonstrated marked cell-surface expression of the TNF alpha-p55 receptor compared with expression of the TNF alpha-p75 receptor on human TSMC. Taken together, our results suggest that TNF alpha modulates agonist-induced calcium transients and induces human TSMC proliferation by specific activation of the TNF alpha-p55 receptor. Further studies addressing the cellular and molecular mechanisms regulating cytokine modulation of airway smooth muscle function may provide new insight into mechanisms that induce airway hyperresponsiveness in asthma.

[1]  C. Bronner,et al.  Ca2+ increase and Ca2+‐influx in human tracheal smooth muscle cells: role of Ca2+ pools controlled by sarco‐endoplasmic reticulum Ca2+‐ATPase 2 isoform , 1995, British journal of pharmacology.

[2]  C. Bronner,et al.  Potentiation by tumour necrosis factor‐α of calcium signals induced by bradykinin and carbachol in human tracheal smooth muscle cells , 1995, British journal of pharmacology.

[3]  H. Loetscher,et al.  Differential responses of fibroblasts from wild-type and TNF-R55-deficient mice to mouse and human TNF-alpha activation. , 1994, Journal of immunology.

[4]  B. Aggarwal,et al.  TNF and its receptor antibody agonist differ in mediation of cellular responses. , 1994, Journal of immunology.

[5]  P. Scheurich,et al.  TNF receptors TR60 and TR80 can mediate apoptosis via induction of distinct signal pathways. , 1994, Journal of immunology.

[6]  E. Puré,et al.  T lymphocytes adhere to airway smooth muscle cells via integrins and CD44 and induce smooth muscle cell DNA synthesis , 1994, The Journal of experimental medicine.

[7]  T. Lee,et al.  Selective enhancement of GM-CSF, TNF-alpha, IL-1 beta and IL-8 production by monocytes and macrophages of asthmatic subjects. , 1994, The European respiratory journal.

[8]  P. Howarth,et al.  Interleukin-4, -5, and -6 and tumor necrosis factor-alpha in normal and asthmatic airways: evidence for the human mast cell as a source of these cytokines. , 1994, American journal of respiratory cell and molecular biology.

[9]  C. Molloy,et al.  Angiotensin II induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. Correlation with the expression of specific endogenous growth factors and reversal by suramin. , 1994, The Journal of clinical investigation.

[10]  D. Banner,et al.  Human tumor necrosis factor alpha (TNF alpha) mutants with exclusive specificity for the 55-kDa or 75-kDa TNF receptors. , 1993, The Journal of biological chemistry.

[11]  C. Bronner,et al.  Tumor necrosis factor alpha potentiates the increase in cytosolic free calcium induced by bradykinin in guinea-pig tracheal smooth muscle cells. , 1993, Comptes rendus de l'Academie des sciences. Serie III, Sciences de la vie.

[12]  S. Hill,et al.  Characteristics of the bradykinin‐induced changes in intracellular calcium ion concentration of single bovine tracheal smooth muscle cells , 1993, British journal of pharmacology.

[13]  R. Pauwels,et al.  The potential role of tumour necrosis factor a in asthma , 1993, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[14]  J. Bonnet,et al.  Tumor necrosis factor-alpha stimulates ICAM-1 expression in human vascular smooth muscle cells. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[15]  A. Inglot,et al.  Elevated release of tumor necrosis factor-alpha and interferon-gamma by bronchoalveolar leukocytes from patients with bronchial asthma. , 1993, The American review of respiratory disease.

[16]  T. Kishimoto,et al.  Cytokine receptors and signal transduction , 1992, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[17]  P. Barnes,et al.  Quantifying proliferation of cultured human and rabbit airway smooth muscle cells in response to serum and platelet-derived growth factor. , 1992, American journal of respiratory cell and molecular biology.

[18]  C. Twort,et al.  The proliferative response of airway smooth muscle , 1992, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[19]  S. Hill,et al.  Bradykinin B2 receptor‐mediated phosphoinositide hydrolysis in bovine cultured tracheal smooth muscle cells , 1992, British journal of pharmacology.

[20]  A. Capron,et al.  Tumor necrosis factor alpha and interleukin-6 production by human mononuclear phagocytes from allergic asthmatics after IgE-dependent stimulation. , 1992, The American review of respiratory disease.

[21]  J. Maclouf,et al.  Regulation of sarco-endoplasmic reticulum Ca(2+)-ATPases during platelet-derived growth factor-induced smooth muscle cell proliferation. , 1992, The Journal of biological chemistry.

[22]  R. Gentz,et al.  Both tumor necrosis factor receptor types mediate proliferative signals in human mononuclear cell activation. , 1992, Journal of immunology.

[23]  R. Abdolrasulnia,et al.  Purification of type I and type II tumor necrosis factor receptors from human lung tissue. , 1992, American journal of respiratory cell and molecular biology.

[24]  D. Broide,et al.  Cytokines in symptomatic asthma airways. , 1992, The Journal of allergy and clinical immunology.

[25]  R. L. Baldwin,et al.  Formation of ion-permeable channels by tumor necrosis factor-alpha. , 1992, Science.

[26]  G. Bernard,et al.  The role of cyclooxygenase products in lung injury induced by tumor necrosis factor in sheep. , 1992, The American review of respiratory disease.

[27]  P. Libby,et al.  Functional significance of human vascular smooth muscle cell-derived interleukin 1 in paracrine and autocrine regulation pathways. , 1992, Experimental cell research.

[28]  R. Pauwels,et al.  Tumor necrosis factor causes bronchial hyperresponsiveness in rats. , 1992, The American review of respiratory disease.

[29]  T. Sung,et al.  Regulation of functional muscarinic receptor expression in tracheal smooth muscle cells. , 1991, The American journal of physiology.

[30]  L. Tartaglia,et al.  The two different receptors for tumor necrosis factor mediate distinct cellular responses. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[31]  M. Kotlikoff,et al.  Receptor‐activated calcium influx in human airway smooth muscle cells. , 1991, The Journal of physiology.

[32]  J. E. Ensor,et al.  Evidence that cultured airway smooth muscle cells contain bradykinin B2 and B3 receptors. , 1991, American journal of respiratory cell and molecular biology.

[33]  G. Ringold,et al.  TNF induces c‐fos via a novel pathway requiring conversion of arachidonic acid to a lipoxygenase metabolite. , 1991, The EMBO journal.

[34]  R. Panettieri,et al.  Histamine stimulates proliferation of airway smooth muscle and induces c-fos expression. , 1990, The American journal of physiology.

[35]  H. Loetscher,et al.  Binding and regulation of cellular functions by monoclonal antibodies against human tumor necrosis factor receptors , 1990, The Journal of experimental medicine.

[36]  C. Smith,et al.  A receptor for tumor necrosis factor defines an unusual family of cellular and viral proteins. , 1990, Science.

[37]  G. Wong,et al.  Molecular cloning and expression of a receptor for human tumor necrosis factor , 1990, Cell.

[38]  H. Tabuchi,et al.  Molecular cloning and expression of the human 55 kd tumor necrosis factor receptor , 1990, Cell.

[39]  H. Schoenfeld,et al.  Identification of two types of tumor necrosis factor receptors on human cell lines by monoclonal antibodies. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[40]  H. Loetscher,et al.  Characterization of binding and biological effects of monoclonal antibodies against a human tumor necrosis factor receptor , 1990, The Journal of experimental medicine.

[41]  R. Tsien,et al.  A new generation of Ca2+ indicators with greatly improved fluorescence properties. , 1985, The Journal of biological chemistry.

[42]  J. Anderson,et al.  A comparison of the quantitative anatomy of the bronchi in normal subjects, in status asthmaticus, in chronic bronchitis, and in emphysema , 1969, Thorax.

[43]  T. Harris,et al.  Tumor necrosis factor alpha modulates mitogenic responses of human cultured airway smooth muscle. , 1995, American journal of respiratory cell and molecular biology.

[44]  M. C. Liu,et al.  Analysis of cytokine transcripts in the bronchoalveolar lavage cells of patients with asthma. , 1993, American journal of respiratory cell and molecular biology.

[45]  N. Morisaki,et al.  Tumour necrosis factor-a can modulate the phenotype of aortic smooth muscle cells , 1993 .

[46]  L. Tartaglia,et al.  Two TNF receptors. , 1992, Immunology today.