SCF promotes the production of IL‑13 via the MEK‑ERK‑CREB signaling pathway in mast cells

Wang,Yimeng; Ma,Hua; Tao,Xiangnan; Luo,Yulan; Wang,Helong; He,Jing; Fang,Qiang; Guo,Shujun; Song,Chuanwang

doi:10.3892/etm.2019.7866

SCF promotes the production of IL‑13 via the MEK‑ERK‑CREB signaling pathway in mast cells

Authors:
- Yimeng Wang
- Hua Ma
- Xiangnan Tao
- Yulan Luo
- Helong Wang
- Jing He
- Qiang Fang
- Shujun Guo
- Chuanwang Song
View Affiliations

Affiliations: Department of Immunology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China, Department of Microbiology and Parasitology, Bengbu Medical College, Bengbu, Anhui 233030, P.R. China
Published online on: August 8, 2019 https://doi.org/10.3892/etm.2019.7866
Pages: 2491-2496
Copyright: © Wang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )

Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )

Cited By (CrossRef): 0 citations Loading Articles...

Abstract

Mast cells serve a key role in the occurrence and development of allergy. As an important growth factor of mast cells, stem cell factor (SCF) has an effect on the apoptosis, chemotaxis, adhesion, degranulation and other biological characteristics of mast cells. However, there are few studies regarding the effect of SCF signal on the production of cytokines from mast cells, particularly Th2 type cytokines. In the present study, the expression and secretion of IL‑13 in P815 cells stimulated by SCF were detected by fluorescence quantitative PCR and ELISA, and western blotting and EMSA were used to detect ERK phosphorylation and activation of CREB in stimulated P815 cells. The results demonstrated that the production of IL‑13 was significantly increased in P815 cells stimulated by SCF (1‑100 ng/ml; P<0.01). There was an obvious phosphorylation of ERK and CREB activation in P815 cells stimulated by SCF (50 ng/ml). Compared with the SCF single stimulation group, the production of IL‑13 was significantly reduced in P815 cells stimulated with U0126 (ERK‑MEK/pathway inhibitor) or H‑89 (CREB inhibitor) combined with SCF stimulation group (P<0.01). However, JSI‑124 (JAK/STAT3 pathway inhibitor), Wortmannin (PI3K/Akt pathway inhibitor) and PDTC (NF‑κB inhibitor) had no effect on the role of SCF promoting the P815 cells producing IL‑13. Therefore, SCF signaling promotes mast cell P815 to produce IL‑13, and this effect is associated with the MEK‑ERK‑CREB signaling pathway.

View Figures

View References

1	Morita H, Saito H, Matsumoto K and Nakae S: Regulatory roles of mast cells in immune responses. Semin Immunopathol. 38:623–629. 2016. View Article : Google Scholar : PubMed/NCBI
2	Huang H, Li Y and Liu B: Transcriptional regulation of mast cell and basophil lineage commitment. Semin Immunopathol. 38:539–548. 2016. View Article : Google Scholar : PubMed/NCBI
3	Boeckxstaens G: Mast cells and inflammatory bowel disease. Curr Opin Pharmacol. 25:45–49. 2015. View Article : Google Scholar : PubMed/NCBI
4	Galli SJ, Nakae S and Tsai M: Mast cells in the development of adaptive immune responses. Nat Immunol. 6:135–142. 2005. View Article : Google Scholar : PubMed/NCBI
5	Gilfillan AM and Tkaczyk C: Integrated signalling pathways for mast-cell activation. Nat Rev Immunol. 6:218–230. 2006. View Article : Google Scholar : PubMed/NCBI
6	Arthur G and Bradding P: New developments in mast cell biology: Clinical implications. Chest. 150:680–693. 2016. View Article : Google Scholar : PubMed/NCBI
7	Cardamone C, Parente R, Feo GD and Triggiani M: Mast cells as effector cells of innate immunity and regulators of adaptive immunity. Immunol Lett. 178:10–14. 2016. View Article : Google Scholar : PubMed/NCBI
8	Savage JH, Courneya JP, Sterba PM, Macglashan DW, Saini SS and Wood RA: Kinetics of mast cell, basophil and oral food challenge responses in omalizumab-treated adults with peanut allergy. J Allergy Clin Immunol. 130:1123–1129.e2. 2012. View Article : Google Scholar : PubMed/NCBI
9	Andersson C, Tufvesson E, Diamant Z and Bjermer L: Revisiting the role of the mast cell in asthma. Curr Opin Pulm Med. 22:10–17. 2016. View Article : Google Scholar : PubMed/NCBI
10	Reber L, Da Silva CA and Frossard N: Stem cell factor and its receptor c-Kit as targets for inflammatory diseases. Eur J Pharmacol. 533:327–340. 2006. View Article : Google Scholar : PubMed/NCBI
11	Lennartsson J and Rönnstrand L: Stem cell factor receptor/c-Kit: From basic science to clinical implications. Physiol Rev. 92:1619–1649. 2012. View Article : Google Scholar : PubMed/NCBI
12	Lorentz A and Bischoff SC: Regulation of human intestinal mast cells by stem cell factor and IL-4. Immunol Rev. 179:57–60. 2001. View Article : Google Scholar : PubMed/NCBI
13	Al-Azzam N, Kondeti V, Duah E, Gombedza F, Thodeti CK and Paruchuri S: Modulation of mast cell proliferative and inflammatory responses by leukotriene d4 and stem cell factor signaling interactions. J Cell Physiol. 230:595–602. 2015. View Article : Google Scholar : PubMed/NCBI
14	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
15	Faber TW, Pullen NA, Fernando JF, Kolawole EM, McLeod JJ, Taruselli M, Williams KL, Rivera KO, Barnstein BO, Conrad DH and Ryan JJ: ADAM10 is required for SCF-induced mast cell migration. Cell Immunol. 290:80–88. 2014. View Article : Google Scholar : PubMed/NCBI
16	Smrž D, Bandara G, Beaven MA, Metcalfe DD and Gilfillan AM: Prevention of F-actin assembly switches the response to SCF from chemotaxis to degranulation in human mast cells. Eur J Immunol. 43:1873–1882. 2013. View Article : Google Scholar : PubMed/NCBI
17	Stankov K, Popovic S and Mikov M: C-KIT signaling in cancer treatment. Curr Pharm Des. 20:2849–2880. 2014. View Article : Google Scholar : PubMed/NCBI
18	O'Laughlin-Bunner B, Radosevic N, Taylor ML, Shivakrupa, DeBerry C, Metcalfe DD, Zhou M, Lowell C and Linnekin D: Lyn is required for normal stem cell factor-induced proliferation and chemotaxis of primary hematopoietic cells. Blood. 98:343–350. 2001. View Article : Google Scholar : PubMed/NCBI
19	Fukao T, Yamada T, Tanabe M, Terauchi Y, Ota T, Takayama T, Asano T, Takeuchi T, Kadowaki T, Hata Ji J and Koyasu S: Selective loss of gastrointestinal mast cells and impaired immunity in PI3K-deficient mice. Nat Immunol. 3:295–304. 2002. View Article : Google Scholar : PubMed/NCBI
20	MacNeil AJ, Junkins RD, Wu Z and Lin TJ: Stem cell factor induces AP-1-dependent mast cell IL-6 production via MAPK kinase 3 activity. J Leukoc Biol. 95:903–915. 2014. View Article : Google Scholar : PubMed/NCBI
21	Moaaz M, Abo El-Nazar S, Abd El-Rahman M and Soliman E: Stem cell factor and interleukin-31 expression: Association with IgE among Egyptian patients with atopic and Nonatopic bronchial asthma. Immunol Invest. 45:87–106. 2016. View Article : Google Scholar : PubMed/NCBI
22	Lei Z, Liu G, Huang Q, Lv M, Zu R, Zhang GM, Feng ZH and Huang B: SCF and IL-31 rather than IL-17 and BAFF are potential indicators in patients with allergic asthma. Allergy. 63:327–332. 2008. View Article : Google Scholar : PubMed/NCBI
23	Samitas K, Delimpoura V, Zervas E and Gaga M: Anti-IgE treatment, airway inflammation and remodelling in severe allergic asthma: Current knowledge andfuture perspectives. Eur Respir Rev. 24:594–601. 2015. View Article : Google Scholar : PubMed/NCBI
24	Anandan C, Nurmatov U, van Schayck OC and Sheikh A: Is the prevalence of asthma declining? Systematic review of epidemiological studies. Allergy. 65:152–167. 2010. View Article : Google Scholar : PubMed/NCBI
25	Bulfone-Paus S and Bahri R: Mast cells as regulators of T cell responses. Front Immunol. 6:3942015. View Article : Google Scholar : PubMed/NCBI
26	Li B, Berman J, Tang JT and Lin TJ: The early growth response factor-1 is involved in stem cell factor (SCF)-induced interleukin 13 production by mast cells, but is dispensable for SCF-dependent mast cell growth. J Biol Chem. 282:22573–22581. 2007. View Article : Google Scholar : PubMed/NCBI
27	Mitchell J, Dimov V and Townley RG: IL-13 and the IL-13 receptor as therapeutic targets for asthma and allergic disease. Curr Opin Investig Drugs. 11:527–534. 2010.PubMed/NCBI
28	Corren J: Role of interleukin-13 in asthma. Curr Allergy Asthma Rep. 13:415–420. 2013. View Article : Google Scholar : PubMed/NCBI