호흡기 상피세포에서 MUC5AC와 MUC5B 발현에 대한 Betulinic Acid의 효과 = Effect of Betulinic Acid on MUC5AC and MUC5B Expression in Airway Epithelial Cells

다국어 초록 (Multilingual Abstract)

Background and Objectives MUC5AC and MUC5B are representative secretory mucin genes in the human airway, whose expressions are increased by a variety of inflammatory mediators. Betulinic acid, a naturally occurring pentacyclic triterpenoid, is known to have an anti-inflammatory property. However, the effects of betulinic acid on mucin secretion of airway epithelial cells still have not been reported. Therefore, in this study, the effect of betulinic acid on inflammatory mediators-induced MUC5AC and MUC5B expressions was investigated in human airway epithelial cells.
Materials and Method In the mucin-producing human NCI-H292 airway epithelial cells, the effects of betulinic acid on interleukin-1β (IL-1β)-, lipopolysaccharide (LPS)-, and phorbol myristate acetate (PMA)-induced MUC5AC and MUC5B expressions were analyzed by reverse transcription-polymerase chain reaction and enzyme-linked immunosorbent assay.
Results Betulinic acid attenuated IL-1β-, LPS-, and PMA-induced MUC5B mRNA and glycoprotein expression in NCI-H292 cells. On the other hand, betulinic acid did not attenuate IL-1β-, and LPS-, but induced PMA-induced MUC5AC mRNA and glycoprotein expressions in NCI-H292 cells.
Conclusion These results suggest that betulinic acid attenuates IL-1β-, LPS-, and PMA-induced MUC5B expression in the airway epithelial cells. Therefore, betulinic acid may modulate a control of mucus-hypersecretion in airway inflammatory diseases.
Korean J Otorhinolaryngol-Head Neck Surg 2014;57(8):526-32

참고문헌 (Reference)

1 이준혁, "호흡기 상피세포에서 MUC5AC와 MUC5B 발현에 대한 Anthocyanidin의 효과" 대한이비인후과학회 56 (56): 291-296, 2013

2 박나경, "인간 호흡기 상피세포에서 MUC5B 발현에 대한 Udenafil의 효과" 대한이비인후과학회 56 (56): 501-505, 2013

3 박상면, "리포다당질 (lipopolysaccharide)에 의한 기관지 점액 생성 기전에서 호중구와 상피세포 성장인자 수용체(epidermal growth factor receptor)의 역할" 대한결핵및호흡기학회 54 (54): 80-90, 2003

4 Ali MS, "Upper airway mucin gene expression: a review" 117 (117): 932-938, 2007

5 Usui S, "Secretory cell differentiation and mucus secretion in cultures of human nasal epithelial cells: use of a monoclonal antibody to study human nasal mucin" 109 (109): 271-277, 2000

6 Yu D, "New developments in natural products-based anti-AIDS research" 27 (27): 108-132, 2007

7 Choi JY, "Isolation of betulinic acid, its methyl ester and guaiane sesquiterpenoids with protein tyrosine phosphatase 1B inhibitory activity from the roots of Saussurea lappa C.B.Clarke" 14 (14): 266-272, 2009

8 Kai H, "Involvement of protein kinase C in mucus secretion by hamster tracheal epithelial cells in culture" 267 (267): L526-L530, 1994

9 김경찬, "HL-60 세포에서 TNF-α에 의한 MCP-1 발현에 미치는 Betulinic Acid의 효과" 대한약학회 52 (52): 37-42, 2008

10 Lee JG, "Expression and regulation of MUC8 & MUC5AC by various cytokines in normal human nasal epithelial cells" 44 (44): 600-605, 2001

11 Nader MA, "Effect of betulinic acid on neutrophil recruitment and inflammatory mediator expression in lipopolysaccharide-induced lung inflammation in rats" 46 (46): 106-113, 2012

12 송은정, "Effect of Epigallocatechin-3-Gallate on PMA-Induced MUC5B Expression in Human Airway Epithelial Cells" 대한이비인후과학회 6 (6): 237-242, 2013

13 Yuan-Chen Wu D, "Distinctive epidermal growth factor receptor/extracellular regulated kinase-independent and -dependent signaling pathways in the induction of airway mucin 5B and mucin 5AC expression by phorbol 12-myristate 13-acetate" 170 (170): 20-32, 2007

14 Pisha E, "Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis" 1 (1): 1046-1051, 1995

15 Fulda S, "Betulinic acid: a new cytotoxic agent against malignant brain-tumor cells" 82 (82): 435-441, 1999

16 Yogeeswari P, "Betulinic acid and its derivatives: a review on their biological properties" 12 (12): 657-666, 2005

17 Liu WK, "Apoptotic activity of betulinic acid derivatives on murine melanoma B16 cell line" 498 (498): 71-78, 2004

18 Fisher DE, "Apoptosis in cancer therapy: crossing the threshold" 78 (78): 539-542, 1994