بررسی اثر پروتئین فعال کننده نوتروفیلی هلیکوباکتر پیلوری بر میزان لکوترینهایC4, B4 و التهاب مجاری هوایی در موش مدل آسم آلرژیک
اثر پروتئین فعال کننده نوتروفیلی هلیکوباکتر بررC4, B4 و التهاب آسم
محورهای موضوعی : نشانگر های زیستی پلاسما
علیرضا خالقی خرمی
1
,
رسول شکری
2
,
Seyyed Shamsadin Athari
3
,
ساناز مهمازی
4
1 -
2 - مرکز تحقیقات زیست شناسی، واحد زنجان، دانشگاه آزاد اسلامی، زنجان، ایران
3 - Department of Immunology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
4 - دانشکده علوم پایه و فنی و مهندسی، دانشگاه آزاد اسلامی واحد زنجان، زنجان ، ایران.
کلید واژه: هلیکوباکتر پیلوری, آسم آلرژیک, پروتئین فعال کننده نوتروفیلی, لکوترین,
چکیده مقاله :
پیش زمینه وهدف پروتئین فعال کننده نوتروفیلی هلیکوباکتر پیلوری (HP-NAP) به عنوان یک ایمونوژن برای برانگیختن پاسخ های آنتی ژنی یا یک تعدیل کننده ایمنی برای تنظیم ایمنی سلول های T عمل می کند. این پروتئین می تواند یک پاسخ Th2 منجر به پاسخ آلرژیک را به سمت پاسخ Th1 سوق دهد .همچنین احتمال می رود بر میزان تولید لکوترینهای C4, B4 و نهایتا بیماری آسم نیز تاثیر بگذارد. هدف از این مطالعه بررسی تاثیر HP-NAP بر میزان لکوترینهای C4, B4 در موش های مدل آسم آلرژیک و مقایسه آن با تاثیرات خود هلیکو باکترپیلوری (Helicobacter pylori) می باشد. مواد وروشها در ابتدا سویه استاندارد هلیکوباکتر پیلوری و پپتید HP-NAP طبق مطالعه قبلی تهیه شد. سپس 40 سر موش نر بالغ Blab c 6 تا 8 هفته‌ای برای مدل‌سازی و ایجاد آسم آلرژیک تهیه و به 4 گروه 10 تایی تقسیم و برای مطالعه تغییرات لکوترینهای مذکورانتخاب شدند. نتایج در اندازه گیری سطح لکوترینهای C4, B4 ،با استفاده از روش الایزا مشاهده شد که سطح C4, B4 گروه آسمی به طور معناداری نسبت به گروه سالم افزایش دارد. در حالی که تیمارها با هلیکوباکتر و HP-NAP منجر به کاهش معنی‌داری در سطوح C4, B4 نسبت به گروه آسمی نشد. نتیجه گیری با توجه به اثرات قوی تر HP-NAP نسبت به خود هلیکو باکتر در کاهش سطح لکوترینهای C4, B4 ، HP-NAP توانست در حیوانات آسمی میزان لکوترینهای C4, B4را کاهش دهد ولی میزان کاهش آن نسبت به گروه آسمی معنی دار نبود .بنابراین مطالعات بیشتر پیشنهاد می گردد.
Background & Aim: Helicobacter pylori neutrophil-activating protein (HP-NAP) acts as an immunogen to elicit antigenic responses or an immunomodulator to regulate T-cell immunity. This protein can lead to a Th2 response, which may result in an allergic response or a Th1 response. It is also likely to affect the production of leukotrienes C4, B4 and finally asthma. The objective of this study is to examine the impact of HP-NAP on the concentration of leukotrienes C4 and B4 in an allergic asthma model in mice and to compare this with the effects of Helicobacter pylori. Materials & Methods: Firstly, the Helicobacter pylori standard strain and HP-NAP peptide were prepared in accordance with the methodology outlined in a previous study. Subsequently, 40 adult Blab c 6 to 8-week-old male mice were prepared for modelling and developing allergic asthma and were divided into four groups of 10. These mice were selected for further study to investigate the changes in the aforementioned leukotrienes. Results: demonstrated that the level of leukotrienes C4 and B4, as measured using the ELISA method, was significantly elevated in the asthmatic group compared to the healthy group. While the treatments with Helicobacter and HP-NAP did not result in a significant decrease in the levels of C4 and B4 compared to the asthmatic group, Conclusion: In light of the more pronounced effects of HP-NAP compared to Helicobacter itself in reducing the level of C4 and B4 leukotrienes, HP-NAP was able to reduce the level of C4 and B4 leukotrienes in asthmatic animals. However, this reduction was not statistically significant when compared to the asthmatic group. Therefore, further studies are recommended.
1. Lin CL, Hsiao G, Wang CC, Lee YL. Imperatorin exerts antiallergic effects in Th2-mediated allergic asthma via induction of IL-10-producing regulatory T cells by modulating the function of dendritic cells. Pharmacological research. 2016 Aug 1; 110:111-21.
2. .Abdelaziz MH, Abdelwahab SF, Wan J, Cai W, Huixuan W, Jianjun C, Kumar KD, Vasudevan A, Sadek A, Su Z, Wang S. Alternatively activated macrophages; a double-edged sword in allergic asthma. Journal of translational medicine. 2020 Dec; 18:1-2
3. Puggioni F, Alves-Correia M, Mohamed MF, Stomeo N, Mager R, Marinoni M, Racca F, Paoletti G, Varricchi G, Giorgis V, Melioli G. Immunostimulants in respiratory diseases: focus on Pidotimod. Multidisciplinary Respiratory Medicine. 2019 Dec; 14:1-0.
4. Ege MJ. The hygiene hypothesis in the age of the microbiome. Annals of the American Thoracic Society. 2017 Nov;14(Supplement 5): S348-53.
5. Miftahussurur M, Nusi IA, Graham DY, Yamaoka Y. Helicobacter, hygiene, atopy, and asthma. Frontiers in microbiology. 2017 Jun 8; 8:1034.
6. Jones MG. Understanding of the molecular mechanisms of allergy. Allergy: Methods and Protocols. 2019:1-5.
7. Daschner A, González Fernández J. Allergy in an evolutionary framework. Journal of Molecular Evolution. 2020 Jan;88(1):66-76.
8. Chen C, Xun P, Tsinovoi C, He K. Accumulated evidence on Helicobacter pylori infection and the risk of asthma: a meta-analysis. Annals of Allergy, Asthma & Immunology. 2017 Aug 1;119(2):137-45.
9. Lambrecht BN, Hammad H. The immunology of asthma. Nature immunology. 2015 Jan;16(1):45-56.
10. Choy DF, Hart KM, Borthwick LA, Shikotra A, Nagarkar DR, Siddiqui S, Jia G, Ohri CM, Doran E, Vannella KM, Butler CA. TH2 and TH17 inflammatory pathways are reciprocally regulated in asthma. Science translational medicine. 2015 Aug 19;7(301):301ra129-.
11. Lim JH, Kim N, Lim SH, Kwon JW, Shin CM, Chang YS, Kim JS, Jung HC, Cho SH. Inverse relationship between Helicobacter pylori infection and asthma among adults younger than 40 years: a cross-sectional study. Medicine. 2016 Feb 1;95(8): e2609.
12. Asayama K, Kobayashi T, D'Alessandro‐Gabazza CN, Toda M, Yasuma T, Fujimoto H, Okano T, Saiki H, Takeshita A, Fujiwara K, Fridman D’Alessandro V. Protein S protects against allergic bronchial asthma by modulating Th1/Th2 balance. Allergy. 2020 Sep;75(9):2267-78.
13. Hwang YH, Kim SJ, Yee ST. Physcion-matured dendritic cells induce the differentiation of Th1 cells. International Journal of Molecular Sciences. 2020 Mar 4;21(5):1753.
14. Palomares O, Yaman G, Azkur AK, Akkoc T, Akdis M, Akdis CA. Role of Treg in immune regulation of allergic diseases. European journal of immunology. 2010 May;40(5):1232-40.
15. Hwang YH, Paik MJ, Yee ST. Diisononyl phthalate induces asthma via modulation of Th1/Th2 equilibrium. Toxicology letters. 2017 Apr 15; 272:49-59.
16. Hong ZW, Yang YC, Pan T, Tzeng HF, Fu HW. Differential effects of DEAE negative mode chromatography and gel-filtration chromatography on the charge status of Helicobacter pylori neutrophil-activating protein. PloS one. 2017 Mar 22;12(3): e0173632.
17. Amedei A, Codolo G, Del Prete G, de Bernard M, D’Elios MM. The effect of Helicobacter pylori on asthma and allergy. Journal of asthma and allergy. 2010 Sep 29:139-47.
18. Santana FP, da Silva RC, Grecco SD, Pinheiro AJ, Caperuto LC, Arantes-Costa FM, Claudio SR, Yoshizaki K, Macchione M, Ribeiro DA, Tibério IF. Inhibition of MAPK and STAT3‐SOCS3 by sakuranetin attenuated chronic allergic airway inflammation in mice. Mediators of inflammation. 2019;2019(1):1356356.
19. Peters-Golden M, Henderson Jr WR. Leukotrienes. New England Journal of Medicine. 2007 Nov 1;357(18):1841-54.
20. Montuschi P, Sala A, Dahlen SE, Folco G. Pharmacological modulation of the leukotriene pathway in allergic airway disease. Drug discovery today. 2007 May 1;12(9-10):404-12.
21. Dahlén SE. Treatment of asthma with antileukotrienes: first line or last resort therapy? European journal of pharmacology. 2006 Mar 8;533(1-3):40-56.
22. Busse W, Kraft M. Cysteinyl leukotrienes in allergic inflammation: strategic target for therapy. Chest. 2005 Apr 1;127(4):1312-26.
23. Folco G, Murphy RC. Eicosanoid transcellular biosynthesis: from cell-cell interactions to in vivo tissue responses. Pharmacological reviews. 2006 Sep 1;58(3):375-88.
24. Hallstrand TS, Henderson Jr WR. An update on the role of leukotrienes in asthma. Current opinion in allergy and clinical immunology. 2010 Feb 1;10(1):60-6.
25. Wenzel SE, Trudeau JB, Kaminsky DA, Cohn J, Martin RJ, Westcott JY. Effect of 5-lipoxygenase inhibition on bronchoconstriction and airway inflammation in nocturnal asthma. American journal of respiratory and critical care medicine. 1995 Sep;152(3):897-905.
26. Wu Z, Mehrabi Nasab E, Arora P, Athari SS. Study effect of probiotics and prebiotics on treatment of OVA-LPS-induced of allergic asthma inflammation and pneumonia by regulating the TLR4/NF-kB signaling pathway. Journal of Translational Medicine. 2022 Mar 16;20(1):130.
27. Li HT, Lin YS, Ye QM, Yang XN, Zou XL, Yang HL, Zhang TT. Airway inflammation and remodeling of cigarette smoking exposure ovalbumin-induced asthma is alleviated by CpG oligodeoxynucleotides via affecting dendritic cell-mediated Th17 polarization. International Immunopharmacology. 2020 May 1; 82:106361.
28. Nadeem A, Ahmad SF, Al-Harbi NO, Ibrahim KE, Siddiqui N, Al-Harbi MM, Attia SM, Bakheet SA. Inhibition of Bruton’s tyrosine kinase and IL-2 inducible T-cell kinase suppresses both neutrophilic and eosinophilic airway inflammation in a cockroach allergen extract-induced mixed granulocytic mouse model of asthma using preventative and therapeutic strategy. Pharmacological Research. 2019 Oct 1; 148:104441.
29. McAleer JP, Kolls JK. Contributions of the intestinal microbiome in lung immunity. European journal of immunology. 2018 Jan;48(1):39-49.
30. He Y, Wen Q, Yao F, Xu D, Huang Y, Wang J. Gut–lung axis: the microbial contributions and clinical implications. Critical reviews in microbiology. 2017 Jan 2;43(1):81-95.
31. Chiu L, Bazin T, Truchetet ME, Schaeverbeke T, Delhaes L, Pradeu T. Protective microbiota: from localized to long-reaching co-immunity. Frontiers in immunology. 2017 Dec 7; 8:1678.
32. Hussain K, Letley DP, Greenaway AB, Kenefeck R, Winter JA, Tomlinson W, Rhead J, Staples E, Kaneko K, Atherton JC, Robinson K. Helicobacter pylori-mediated protection from allergy is associated with IL-10-secreting peripheral blood regulatory T cells. Frontiers in immunology. 2016 Mar 7; 7:71.
33. Kyburz A, Fallegger A, Zhang X, Altobelli A, Artola-Boran M, Borbet T, Urban S, Paul P, Münz C, Floess S, Huehn J. Transmaternal Helicobacter pylori exposure reduces allergic airway inflammation in offspring through regulatory T cells. Journal of allergy and clinical immunology. 2019 Apr 1;143(4):1496-512.
34. Lee DC, Tay NQ, Thian M, Prabhu N, Furuhashi K, Kemeny DM. Prior exposure to inhaled allergen enhances anti-viral immunity and T cell priming by dendritic cells. PLoS One. 2018 Jan 2;13(1): e0190063.
35. Amon L, Lehmann CH, Baranska A, Schoen J, Heger L, Dudziak D. Transcriptional control of dendritic cell development and functions. International review of cell and molecular biology. 2019 Jan 1; 349:55-151.
36. Oertli M, Müller A. Helicobacter pylori targets dendritic cells to induce immune tolerance, promote persistence and confer protection against allergic asthma. Gut microbes. 2012 Nov 16;3(6):566-71.
37. Arnold IC, Hitzler I, Müller A. The immunomodulatory properties of Helicobacter pylori confer protection against allergic and chronic inflammatory disorders. Frontiers in cellular and infection microbiology. 2012 Feb 16; 2:10.
38. Liu X, Fu G, Ji Z, Huang X, Ding C, Jiang H,et al. A recombinant DNA plasmid encoding the sIL-4R-NAP fusion protein suppress airway inflammation in an OVA-induced mouse model of asthma. Inflammation. 2016; 39(4):1434–40.