Document Type : Original Article
Authors
1 School of Life Sciences, Zhengzhou University, Zhengzhou 450001, Henan, China.
2 Frontier Science Center for Synthetic Biology and Key Laboratory of Systems Bioengineering (Ministry of Education), School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China.
Abstract
Background: Allergic dermatitis (AD) is an inflammatory skin disease that arises from abnormal T lymphocyte activation. A recombinant fusion protein comprising Helicobacter pylori neutrophil-activating protein and maltose binding protein, rMBP-NAP, has been documented as a novel immunomodulatory TLR agonist.
Objective: To explore the effect of the rMBP-NAP on the OXA-induced AD in a mouse model and clarify the possible action mechanism.
Methods: The AD animal model was induced by repeated administration of oxazolone (OXA) in BALB/c mice. H&E staining was used to analyze the ear epidermis thickness and the number of infiltrating inflammatory cells. TB staining was used to detect mast cell infiltration in the ear tissue. ELISA was used to analyze the secretion of cytokines IL-4 and IFN-γ in peripheral blood. qRT-PCR was used to determine the expression levels of IL-4, IFN-γ, and IL-13 in ear tissue.
Results: OXA induced the establishment of an AD model. After the rMBP-NAP treatment, the thickness of the ear tissue and the number of mast cells infiltrated in AD mice reduced, and the serum and ear tissue levels of IL-4 and IFN-γ increased, but the ratio of IFN-γ (rMBP-NAP group)/IL-4 (rMBP-NAP group) was greater than the ratio of IFN-γ (sensitized group)/IL-4 (sensitized group).
Conclusion: The rMBP-NAP improved the disease symptoms including skin lesions in AD, alleviated the inflammation in ear tissue, and restored the Th1/2 balance by inducing a shift from the Th2 to the Th1 response. The results of our work support the use of rMBP-NAP as an immunomodulator for AD treatment in future investigations.
Keywords
- Mu Z, Zhao Y, Liu X, Chang C, Zhang J. Molecular biology of atopic dermatitis. Clin Rev Allergy Immunol.2014;47:193-218.
- Kabashima K, Otsuka A, Nomura T. Linking air pollution to atopic dermatitis. Nat Immunol.2016;18:5-6.
- Henriksen L, Simonsen J, Haerskjold A, Linder M, Kieler H, Thomsen S, Stensballe L. Incidence rates of atopic dermatitis, asthma, and allergic rhinoconjunctivitis in Danish and Swedish children. J Allergy Clin Immunol.2015;136:360-366 e362.
- Yang G, Seok JK, Kang HC, Cho YY, Lee HS, Lee JY. Skin Barrier Abnormalities and Immune Dysfunction in Atopic Dermatitis. Int J Mol Sci.2020;21.
- Cheung PF, Wong CK, Ho AW, Hu S, Chen DP, Lam CW. Activation of human eosinophils and epidermal keratinocytes by Th2 cytokine IL-31: implication for the immunopathogenesis of atopic dermatitis. Int Immunol.2010;22:453-467.
- Kawakami T, Ando T, Kimura M, Wilson BS, Kawakami Y. Mast cells in atopic dermatitis. Curr Opin Immunol.2009;21:666-678.
- Venturelli N, Lexmond W, Ohsaki A, Nurko S, Karasuyama H, Fiebiger E, Oyoshi M. Allergic skin sensitization promotes eosinophilic esophagitis through the IL-33-basophil axis in mice. J Allergy Clin Immunol.2016;138:1367-1380 e1365.
- Kubo A, Nagao K, Amagai M. Epidermal barrier dysfunction and cutaneous sensitization in atopic diseases. J Clin Invest.2012;122:440-447.
- Hon KL, Pong NH, Wang SS, Lee VW, Luk NM, Leung TF. Acceptability and efficacy of an emollient containing ceramide-precursor lipids and moisturizing factors for atopic dermatitis in pediatric patients. Drugs R D.2013;13:37-42.
- Matsumoto A, Murota H, Terao M, Katayama I. Attenuated Activation of Homeostatic Glucocorticoid in Keratinocytes Induces Alloknesis via Aberrant Artemin Production. J Invest Dermatol.2018;138:1491-1500.
- Jensen JM, Pfeiffer S, Witt M, Neumann C, Weichenthal M. Different effects of pimecrolimus and betamethasone on the skin barrier in patients with atopic dermatitis. J Allergy Clin Immunol.2009;124:R19-28.
- Wang T, Liu X.L, Ji Z.Y, Men Y.L, Du M.X, Ding C, Wu Y.H, Liu X, Kang Q.Z. Antitumor and immunomodulatory effects of recombinant fusion protein rMBP-NAP through TLR-2 dependent mechanism in tumor bearing mice. Int Immunopharmacol.2015;29:876-883.
- Amedei A, Cappom A, Codolo G. The neutrophil-activating protein of Helicobacter pylori promotes Th1 immune responses. Journal of Clinical Investigation.2006;116:1092-1101.
- D'Elios MM, Amedei A, Cappon A, Del Prete G, de Bernard M. The neutrophil-activating protein of Helicobacter pylori (HP-NAP) as an immune modulating agent. Fems Immunology and Medical Microbiology.2007;50:157-164.
- Zhao X.X, Ni W.H, Zhang Q.Y, Wang F.L. Maltose-binding protein isolated from Escherichia coli induces Toll-like receptor 2-mediated viability in U937 cells. Clinical & Translational Oncology.2011;13:509-518.
- Guo X, Ding C, Lu J.K, Zhou T.T, Liang T.T, Ji Z.Y, Xie P, Liu X, Kang Q.Z. HP-NAP ameliorates OXA-induced atopic dermatitis symptoms in mice. Immunopharmacology and Immunotoxicology.2020;42:416-422.
- Kang Q.Z, Duan G.C, Fan Q.T, Xi Y. Fusion expression of Helicobacter pylori neutrophil-activating protein in E. coli, World J. Gastroenterol. 2005;03:454–456.
- Liu F-T, Goodarzi H, Chen H-Y. IgE, Mast Cells, and Eosinophils in Atopic Dermatitis. Clinical Reviews in Allergy & Immunology.2011;41:298-310.
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