Emodin attenuates A23187-induced mast cell degranulation and tumor necrosis factor-α secretion through protein kinase C and IκB kinase 2 signaling.
Mast cells are known to play a pivotal role in allergic diseases. Cross-linking of the high-affinity IgE receptor (FcεRI) is known to be one of the major causes that lead to degranulation and allergic inflammation. An increase in intracellular calcium (Ca(2+)) concentration also triggers degranulation, bypassing receptor activation. Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is known to exhibit a variety of pharmacological activities including anti-allergic effects. However, the detailed molecular mechanisms involved in exhibiting anti-allergic effects by emodin were remained to be clarified. In the present investigation we report the regulatory function of emodin on the allergic signal mediators through Ca(2+) ionophore activation in mast cells. Emodin significantly inhibited A23187-induced tumor necrosis factor-α production and degranulation through the attenuation of protein kinase C, IκB kinase 2, and soluble N-ethylmaleimide-sensitive fusion factor attachment protein receptor complex formation, bypassing FcεRI activation. Data from our study indicated that emodin acts by regulating multiple signaling pathways in inhibiting the allergic reactions in mast cells.
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
Dong-Young
DY
Kim
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
Tae-Bong
TB
Kang
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
Do-Wan
DW
Shim
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
Xiao
X
Sun
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
Ji-Won
JW
Han
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
Young-Eun
YE
Ji
Division of Biological Science and Technology, Yonsei University, Wonju, Republic of Korea.
Tack-Joong
TJ
Kim
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea.
Sushruta
S
Koppula
Department of Biotechnology, College of Biomedical & Health Science, Research Institute of Inflammatory Diseases, Konkuk University, Chungju, Chungbuk 380-701, Republic of Korea. Electronic address: kwangho@kku.ac.kr.
Kwang-Ho
KH
Lee
D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D015550:Cell Degranulation / Q000187:drug effects*; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D004642:Emodin / Q000494:pharmacology*; D005260:Female; D051550:I-kappa B Kinase / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008407:Mast Cells / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D050766:Qb-SNARE Proteins / Q000378:metabolism; D050767:Qc-SNARE Proteins / Q000378:metabolism; D051381:Rats; D017455:Receptors, IgE / Q000378:metabolism; D050600:SNARE Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000072377:Syk Kinase; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D047908:Intracellular Signaling Peptides and Proteins; D050766:Qb-SNARE Proteins; D050767:Qc-SNARE Proteins; D017455:Receptors, IgE; D050600:SNARE Proteins; C107017:Snap23 protein, mouse; D014409:Tumor Necrosis Factor-alpha; D015847:Interleukin-4; D000001:Calcimycin; D011505:Protein-Tyrosine Kinases; D000072377:Syk Kinase; C000606897:Syk protein, mouse; C000606898:Syk protein, rat; D051550:I-kappa B Kinase; D011493:Protein Kinase C; D004642:Emodin; D002118:Calcium
Allergy; Emodin; IκB kinase-2; Mast cells; Protein kinase C; SNARE complex