Blockade of ankyrin repeat-rich membrane spanning protein modulates extracellular signal‑regulated kinase expression and inhibits allergic inflammation in ovalbumin‑sensitized mice

Ni,Xiuqin; Li,Xing; Tao,Shuhua; Xu,Minghui; Ma,Hongmei; Wang,Xiuli

doi:10.3892/br.2013.120

Blockade of ankyrin repeat-rich membrane spanning protein modulates extracellular signal‑regulated kinase expression and inhibits allergic inflammation in ovalbumin‑sensitized mice

Authors:
- Xiuqin Ni
- Xing Li
- Shuhua Tao
- Minghui Xu
- Hongmei Ma
- Xiuli Wang
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Affiliations: Department of Anatomy, Harbin Medical University‑Daqing, Daqing, Heilongjiang 163319, P.R. China, Department of Nephrology, Daqing People's Hospital, Daqing, Heilongjiang 163310, P.R. China, Biopharmaceutical Institute, Heilongjiang Academy of Medical Sciences, Harbin, Heilongjiang 150081, P.R. China
Published online on: May 30, 2013 https://doi.org/10.3892/br.2013.120
Pages: 674-678

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Abstract

Ankyrin repeat‑rich membrane spanning protein (ARMS), also known as kinase D‑interacting substrate of 220 kDa (Kidins220), is a transmembrane protein that has been reported to be involved in the pathogenesis of asthma through the nerve growth factor (NGF)̸tyrosine kinase A (TrkA) receptor signaling pathway. To investigate whether NGF/TrkA‑Kidins220/ARMS‑extracellular signal‑regulated kinase (ERK) signaling is activated in airway inflammation of asthma, BALB/c mice were sensitized and challenged with ovalbumin (OVA). The effects of Kidins220/ARMS on ERK, interleukin (IL)‑1β, IL‑4 and tumor necrosis factor (TNF)‑α in lung tissues following the allergic airway challenge in mice were assessed by administering anti‑ARMS antibody to the mice. Pathological changes in the bronchi and lung tissues were examined via hematoxylin and eosin staining. The phosphorylated ERK, IL‑1β, IL‑4 and TNF‑α levels were determined using western blot analysis and ELISA and were found to be overexpressed in lung tissues following the allergen challenge. Moreover, after the mice were treated with anti‑NGF, anti‑TrkA or anti‑ARMS, the levels of Kidins220/ARMS, phosphorylated ERK, IL‑1β, IL‑4, TNF‑α and allergen‑induced airway inflammation were downregulated. These results suggested that NGF̸TrkA‑Kidins220̸ARMS‑ERK signaling was activated in airway inflammation induced by the allergic airway challenge, possibly representing a new mechanism in asthma.

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1	Edwards MR, Bartlett NW, Clarke D, Birrell M, Belvisi M and Johnston SL: Targeting the NF-κB pathway in asthma and chronic obstructive pulmonary disease. Pharmacol Ther. 121:1–13. 2009.
2	Kong H, Boulter J, Weber JL, Lai C and Chao MV: An evolutionarily conserved transmembrane protein that is a novel downstream target of neurotrophin and ephrin receptors. J Neurosci. 21:176–185. 2001.PubMed/NCBI
3	Arevalo JC, Yano H, Teng KK and Chao MV: A unique pathway for sustained neurotrophin signaling through an ankyrin-rich membrane-spanning protein. EMBO J. 23:2358–2368. 2004. View Article : Google Scholar : PubMed/NCBI
4	Davids RJ: The mitogen-activated protein kinase signal transduction pathway. J Biol Chem. 268:14553–14556. 1993.PubMed/NCBI
5	Robinson MJ and Cobb MH: Mitogen-activated protein kinase pathways. Curr Opin Cell Biol. 9:180–186. 1997. View Article : Google Scholar : PubMed/NCBI
6	Hallsworth MP, Moir LM, Lai D and Hirst SJ: Inhibitors of mitogen-activated protein kinases differentially regulate eosinophil-activating cytokine release from human airway smooth muscle. Am J Respir Crit Care Med. 164:688–697. 2001. View Article : Google Scholar
7	Kumar A, Lnu S, Malya R, Barron D, Moore J, Corry DB and Boriek AM: Mechanical stretch activates nuclear factor-κB, activator protein-1, and mitogen-activated protein kinases in lung parenchyma: implications in asthma. FASEB J. 17:1800–1811. 2003.
8	Ni X, Li X, Fang X, Li N, Cui W and Zhang B: NGF/TrkA-mediated Kidins220/ARMS signaling activated in the allergic airway challenge in mice. Ann Allergy Asthma Immunol. 105:299–306. 2010. View Article : Google Scholar : PubMed/NCBI
9	Ni X, Li X, Fang X, Li N, Cui W, Zhang B and Liu Y: Kidins220/ARMS contributes to airway inflammation and hyper-responsiveness in OVA-sensitized mice. Respir Physiol Neurobiol. 175:97–103. 2011. View Article : Google Scholar : PubMed/NCBI
10	Ying S, Zhang G, Gu S and Zhao J: How much do we know about atopic asthma: where are we now? Cell Mol Immunol. 3:321–332. 2006.PubMed/NCBI
11	Gosset P, Tsicopoulos A, Wallaert B, Vannimenus C, Joseph M, Tonnel AB and Capron A: Increased secretion of tumor necrosis factor alpha and interleukin-6 by alveolar macrophages consecutive to the development of the late asthmatic reaction. J Allergy Clin Immunol. 88:561–571. 1991. View Article : Google Scholar : PubMed/NCBI
12	Wills-Karp M, Uchida Y, Lee JY, Jinot J, Hirata A and Hirata F: Organ culture with proinflammatory cytokines reproduces impairment of the beta-adrenoceptor-mediated relaxation in tracheas of a guinea pig antigen model. Am J Respir Cell Mol Biol. 8:153–159. 1993. View Article : Google Scholar
13	Jie Z, Jin M, Cai Y, et al: The effects of Th2 cytokines on the expression of ADAM33 in allergen-induced chronic airway inflammation. Respir Physiol Neurobiol. 168:289–294. 2009. View Article : Google Scholar : PubMed/NCBI
14	Yoshinaka T, Nishii K, Yamada K, et al: Identification and characterization of novel mouse and human ADAM33s with potential metalloprotease activity. Gene. 282:227–236. 2002. View Article : Google Scholar : PubMed/NCBI
15	Averill S, Delcroix JD, Michael GJ, Tomlinson DR, Fernyhough P and Priestley JV: Nerve growth factor modulates the activation status and fast axonal transport of ERK1/2 in adult nociceptive neurons. Mol Cell Neurosci. 18:183–196. 2001. View Article : Google Scholar : PubMed/NCBI
16	Boehme SA, Sullivan SK, Crowe PD, Santos M, Conlon PJ, Sriramarao P and Bacon KB: Activation of mitogen-activated protein kinase regulates eotaxin-induced eosinophil migration. J Immunol. 163:1611–1618. 1999.PubMed/NCBI
17	Hoffmeyer A, Grosse-Wilde A, Flory E, Neufeld B, Kunz M, Rapp UR and Ludwig S: Different mitogen-activated protein kinase signaling pathways cooperate to regulate tumor necrosis factor alpha gene expression in T lymphocytes. J Biol Chem. 274:4319–4327. 1999. View Article : Google Scholar
18	Maruoka S, Hashimoto S, Gon Y, Takeshita I and Horie T: PAF-induced RANTES production by human airway smooth muscle cells requires both p38 MAP kinase and Erk. Am J Respir Crit Care Med. 161:922–929. 2000. View Article : Google Scholar : PubMed/NCBI
19	Jean-Mairet RM, López-Menéndez C, Sánchez-Ruiloba L, et al: The neuronal protein Kidins220/ARMS associates with ICAM-3 and other uropod components and regulates T-cell motility. Eur J Immunol. 41:1035–1046. 2011. View Article : Google Scholar : PubMed/NCBI
20	Duan W, Chan JH, Wong CH, Leung BP and Wong WS: Anti-inflammatory effects of mitogen-activated protein kinase kinase inhibitor U0126 in an asthma mouse model. J Immunol. 172:7053–7059. 2004. View Article : Google Scholar : PubMed/NCBI
21	Elwood W, Lotvall JO, Barnes PJ and Chung KF: Characterization of allergen-induced bronchial hyperresponsiveness and airway inflammation in actively sensitized brown-Norway rats. J Allergy Clin Immunol. 88:951–960. 1991. View Article : Google Scholar : PubMed/NCBI
22	Vanacker NJ, Palmans E, Kips JC and Pauwels RA: Fluticasone inhibits but does not reverse allergen-induced structural airway changes. Am J Respir Crit Care Med. 163:674–679. 2001. View Article : Google Scholar : PubMed/NCBI
23	Braun A, Appel E, Baruch R, et al: Role of nerve growth factor in a mouse model of allergic airway inflammation and asthma. Eur J Immunol. 28:3240–3251. 1998. View Article : Google Scholar : PubMed/NCBI
24	Glaab T, Hoymann HG, Hecht M, et al: Effect of anti-nerve growth factor on early and late airway responses in allergic rats. Allergy. 58:900–904. 2003. View Article : Google Scholar : PubMed/NCBI
25	Nagai T, Arai Y, Emori M, Nunome SY, Yabe T, Takeda T and Yamada H: Anti-allergic activity of a Kampo (Japanese herbal) medicine ‘Sho-seiryu-to (Xiao-Qing-Long-Tang)’ on airway inflammation in a mouse model. Int Immunopharmacol. 4:1353–1365. 2004.
26	de Vries A, Engels F, Henricks PA, et al: Airway hyper-responsiveness in allergic asthma in guinea-pigs is mediated by nerve growth factor via the induction of substance P: a potential role for trkA. Clin Exp Allergy. 36:1192–1200. 2006.PubMed/NCBI
27	Li L, Kong L, Fang X, et al: SH2-Bβ expression in alveolar macrophages in BAL fluid of asthmatic guinea pigs and its role in NGF-TrkA-mediated asthma. Respirology. 14:60–68. 2009.
28	Frossard N, Naline E, Olgart Hoglund C, Georges O and Advenier C: Nerve growth factor is released by IL-1beta and induces hyperresponsiveness of the human isolated bronchus. Eur Respir J. 26:15–20. 2005. View Article : Google Scholar : PubMed/NCBI
29	Nockher WA and Renz H: Neurotrophins in allergic diseases: from neuronal growth factors to intercellular signaling molecules. J Allergy Clin Immunol. 117:583–589. 2006. View Article : Google Scholar : PubMed/NCBI
30	Iglesias T, Cabrera-Poch N, Mitchell MP, Naven TJ, Rozengurt E and Schiavo G: Identification and cloning of Kidins220, a novel neuronal substrate of protein kinase D. J Biol Chem. 275:40048–40056. 2000. View Article : Google Scholar : PubMed/NCBI
31	Chang L and Karin M: Mammalian MAP kinase signalling cascades. Nature. 410:37–40. 2001. View Article : Google Scholar : PubMed/NCBI
32	Neubrand VE, Cesca F, Benfenati F and Schiavo G: Kidins220/ARMS as a functional mediator of multiple receptor signalling pathways. J Cell Sci. 125(Pt 8): 1845–1854. 2012. View Article : Google Scholar : PubMed/NCBI
33	Chung KF: Airway smooth muscle cells: contributing to and regulating airway mucosal inflammation? Eur Respir J. 15:961–968. 2000. View Article : Google Scholar : PubMed/NCBI
34	Moore PE, Church TL, Chism DD, Panettieri RA Jr and Shore SA: IL-13 and IL-4 cause eotaxin release in human airway smooth muscle cells: a role for ERK. Am J Physiol Lung Cell Mol Physiol. 282:L847–L853. 2002. View Article : Google Scholar : PubMed/NCBI
35	Jorritsma PJ, Brogdon JL and Bottomly K: Role of TCR-induced extracellular signal-regulated kinase activation in the regulation of early IL-4 expression in naive CD4⁺T cells. J Immunol. 170:2427–2434. 2003. View Article : Google Scholar : PubMed/NCBI
36	Finkelman FD, Hogan SP, Hershey GK, Rothenberg ME and Wills-Karp M: Importance of cytokines in murine allergic airway disease and human asthma. J Immunol. 184:1663–1674. 2010. View Article : Google Scholar : PubMed/NCBI
37	Tillie-Leblond I, Pugin J, Marquette CH, et al: Balance between pro-inflammatory cytokines and their inhibitors in bronchial lavage from patients with status asthmaticus. Am J Respir Crit Care Med. 159:487–494. 1999. View Article : Google Scholar : PubMed/NCBI
38	Zimmermann N, Hershey GK, Foster PS and Rothenberg ME: Chemokines in asthma: cooperative interaction between chemokines and IL-13. J Allergy Clin Immunol. 111:227–242. 2003. View Article : Google Scholar : PubMed/NCBI
39	Secor ER, Carson WF, Singh A, Pensa M, Guernsey LA, Schramm CM and Thrall RS: Oral bromelain attenuates inflammation in an ovalbum-induced murine model of asthma. Evid Based Complement Alternat Med. 5:61–69. 2008. View Article : Google Scholar : PubMed/NCBI
40	Yin H, Jin XB, Gong Q, Yang H, Hu LY, Gong FL and Zhu JY: Fructose-1,6-diphosphate attenuates acute lung injury induced by lipopolysaccharide in mice. Int Immunopharmacol. 8:1842–1847. 2008. View Article : Google Scholar : PubMed/NCBI
41	Nakae S, Lunderius C, Ho LH, Schafer B, Tsai M and Galli SJ: TNF can contribute to multiple features of ovalbumin-induced allergic inflammation of the airways in mice. J Allergy Clin Immunol. 119:680–686. 2007. View Article : Google Scholar : PubMed/NCBI
42	Cui CH, Adachi T, Oyamada H, et al: The role of mitogen-activated protein kinases in eotaxin-induced cytokine production from bronchial epithelial cells. Am J Respir Cell Mol Biol. 27:329–335. 2002. View Article : Google Scholar : PubMed/NCBI
43	Lorentz A, Klopp I, Gebhardt T, Manns MP and Bischoff SC: Role of activator protein 1, nuclear factor-κB, and nuclear factor of activated T cells in IgE receptor-mediated cytokine expression in mature human mast cells. J Allergy Clin Immunol. 111:1062–1068. 2003.
44	Langdon C, Kerr C, Tong L and Richards CD: Oncostatin M regulates eotaxin expression in fibroblasts and eosinophilic inflammation in C57BL/6 mice. J Immunol. 170:548–555. 2003. View Article : Google Scholar : PubMed/NCBI