Sopoongsan Inhibits Mast Cell-Mediated Anaphylactic Reactions and Inflammatory Cytokine Secretion

Background: Mast cells are key effector cells in the early-phase allergic inflammation and in diverse immunological and pathological processes. Sopoongsan (SPS), a traditional Korean medicine, has been used as therapeutics for allergic diseases such as atopic dermatitis (AD). The precise effect in experimental models of SPS, however, remains unknown. In this report, we investigated the effect of SPS on mast cell-mediated anaphylactic reactions and cytokine production in in vivo and in vitro murine models. Methods: Compound 48/80-induced histamine and ear swelling were measured with the various concentrations of SPS. The amount of dye was determined colorimetrically after antidinitrophenyl IgE antibody-induced passive cutaneous anaphylaxis reaction. Secretion of tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8) and IL-6 in supernatants from HMC-1 cells was measured by a sandwich enzyme-linked immunosorbent assay. The expression level of nuclear factor (NF)-ĸB/Rel A in the nucleus and the activation of mitogen-activated protein kinases (MAPKs) were examined by Western blot analysis. Results: SPS inhibited the degranulation and histamine release from the rat peritoneal mast cells activated by compound 48/80. Compound 48/80-induced ear swelling was significantly reduced. SPS also showed an inhibitory effect of passive cutaneous anaphylaxis reaction. Significantly reduced levels (p < 0.05) of TNF-α, IL-8 and IL-6 were observed in the human mast cell line with SPS and SPS components. In addition, SPS inhibited an increase of NF-ĸB and extracellular signal-regulated kinase 1/2 activity. Conclusions: These findings suggest that SPS has an inhibitory effect on atopic allergic reaction and this might be useful for the clinical application to treat allergic diseases such as AD.

[1]  Möller,et al.  Comparative cytokine gene expression: regulation and release by human mast cells , 1998, Immunology.

[2]  R. Gereau,et al.  Inflammation persistently enhances nocifensive behaviors mediated by spinal group I mGluRs through sustained ERK activation , 2004, Pain.

[3]  L. Ackermann,et al.  Mast cells of psoriatic and atopic dermatitis skin are positive for TNF-α and their degranulation is associated with expression of ICAM-1 in the epidermis , 1998, Archives of Dermatological Research.

[4]  H. Kim,et al.  Effect of Kumhwang-San on anaphylactic reaction in a murine model. , 1999, Immunopharmacology and immunotoxicology.

[5]  E. Morii,et al.  Role of mast cell histamine in the formation of rat paw edema: a microdialysis study. , 1997, European journal of pharmacology.

[6]  M. Vieytes,et al.  Functional compartments in rat mast cells for cAMP and calcium on histamine release. , 2000, Cellular signalling.

[7]  G. Nilsson,et al.  Activation of mast cells by immunoglobulin E‐receptor cross‐linkage, but not through adenosine receptors, induces A1 expression and promotes survival , 2003, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[8]  P. A. Shore,et al.  A method for the fluorometric assay of histamine in tissues. , 1959, The Journal of pharmacology and experimental therapeutics.

[9]  K. Austen,et al.  Native heparin from rat peritoneal mast cells. , 1977, The Journal of biological chemistry.

[10]  H. Shionoya,et al.  A New Method for Extraction of Extravasated Dye in the Skin and the Influence of Fasting Stress on Passive Cutaneous Anaphylaxis in Guinea Pigs and Rats * , 1978, Microbiology and immunology.

[11]  J. Piette,et al.  Activation of the NF-kappaB transcription factor in a T-lymphocytic cell line by hypochlorous acid. , 1997, The Biochemical journal.

[12]  N. Soter.  Morphology of atopic eczema , 1980, Allergy.

[13]  I. Kimber,et al.  Differential regulation of mast cell cytokines by both dexamethasone and the p38 mitogen‐activated protein kinase (MAPK) inhibitor SB203580 , 2004, Clinical and experimental immunology.

[14]  Seung-Heon Hong,et al.  Forsythia fructus Inhibits the Mast-Cell-Mediated Allergic Inflammatory Reactions , 2003, Inflammation.

[15]  M. White.  Mediators of inflammation and the inflammatory process. , 1999, The Journal of allergy and clinical immunology.

[16]  M. Karin,et al.  Nuclear factor-kappaB: a pivotal transcription factor in chronic inflammatory diseases. , 1997, The New England journal of medicine.

[17]  J. Bockaert,et al.  Interaction of substance P, compound 4880 and mastoparan with the α-subunit C-terminus of G protein , 1990 .

[18]  Y. Okayama,et al.  Human mast cells and basophils as sources of cytokines , 2000, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[19]  M. May,et al.  Signal transduction through NF-kappa B. , 1998, Immunology today.

[20]  P. Baeuerle,et al.  Function and activation of NF-kappa B in the immune system. , 1994, Annual review of immunology.

[21]  Hyung‐Min Kim,et al.  Tongkyutang inhibits mast cell-dependent allergic reactions and inflammatory cytokines secretion. , 2002, Clinica chimica acta; international journal of clinical chemistry.

[22]  R. Vender,et al.  Antihistamines in the Treatment of Atopic Dermatitis , 2003 .

[23]  G L Johnson,et al.  Organization and regulation of mitogen-activated protein kinase signaling pathways. , 1999, Current opinion in cell biology.

[24]  S. Galli,et al.  New concepts about the mast cell. , 1993, The New England journal of medicine.

[25]  S. Ghosh,et al.  Signal transduction through NF-κB , 1998 .