ارزیابی اثرات ویتامین D3 فعال بر میزان بیان ژن‌های پپتیدهای ضدمیکروبی در پنومونی تجربی گوساله‌ها
محورهای موضوعی :
آسیب شناسی درمانگاهی دامپزشکی
پریسا اصغرپور
1
,
زهره افتخاری
2
,
محمدقلی نادعلیان
3
,
غلامرضا نیکبخت بروجنی
4
,
محمد رضا مخبر دزفولی
5
1 - دانش‌آموخته دکترای تخصصی بیماری‌های داخلی دام‌های بزرگ، دانشکده علوم تخصصی دامپزشکی، واحد علوم و تحقیقات تهران، دانشگاه آزاد اسلامی، تهران، ایران.
2 - استادیار بخش کنترل کیفیت، مجتمع تولیدی تحقیقاتی انستیتو پاستور ایران، انستیتو پاستور ایران، البرز، ایران.
3 - استاد گروه بیماری‌های داخلی، دانشکده دامپزشکی، دانشگاه تهران، تهران، ایران.
4 - استاد گروه میکروبیولوژی، دانشکده دامپزشکی، دانشگاه تهران، تهران، ایران.
5 - استاد گروه بیماری‌های داخلی، دانشکده دامپزشکی، دانشگاه تهران، تهران، ایران؛ پژوهشکده تحقیقات زیست‌پزشکی، دانشکده دامپزشکی، دانشگاه تهران، تهران، ایران.
تاریخ دریافت : 1400/04/27
تاریخ پذیرش : 1400/09/02
تاریخ انتشار : 1400/08/01
کلید واژه:
پاستورلا مولتوسیدا,
پنومونی,
ویتامین D3,
پپتیدهای ضدمیکروبی,
چکیده مقاله :
شیوع پنومونی در گله ها به دلیل عوامل بیماری زای مختلف رخ می دهد. ویتامین D3 با اثر بر سلول های مختلف و تحریک عملکرد بیولوژیکی آن ها، پپتیدهای ضدمیکروبی را تحریک می کند. در مطالعه حاضر، اثرات ویتامین D3 بر بیان ژن های پپتیدهای ضد میکروبی در پاستورلوزیس تجربی در گوساله ها ارزیابی شد. بدین منظور، 10 رأس گوساله نر نژاد هلشتاین (4-2 ماهه) به طور تصادفی به 2 گروه تقسیم شدند. باکتری پاستورلا مولتوسیدا با رقت 3 × 109 CFU / mL در نای همه گوساله ها تلقیح و بعد از تأیید پنومونی، ویتامین D3 فقط به حیوانات گروه درمان تزریق شد. نمونه های خون از گوساله های هر 2 گروه در فواصل زمانی مختلف اخذ و سلول های تک‌هسته ای خون محیطی برای ارزیابی بیان ژن های پپتیدهای ضدمیکروبی شاملCD4 (cluster of differentiation 4)، دفنسین و کاتالیسیدین جداسازی شد. همچنین برای ارزیابی سلول های ریه، لاواژ برونکوآلوئولار انجام شد. در شرایط درون تنی، بیان ژن های دفنسین و CD4، تفاوت آماری معنی داری را در گروه های کنترل و درمان در 48 ، 72 ، 96 و 120 ساعت پس از زمان چالش نشان دادند (05/0p<). علاوه بر این در شرایط برون تنی، افزایش بیان ژن های کاتالیسیدین، دفنسین و CD4 در غلظت 7-10 مولار از ویتامین D3 مشاهده شد. طبق نتایج مطالعه حاضر، مشخص شد که ویتامین D3 دارای اثرات مثبتی بر سیستم ایمنی می‌باشد که بصورت بهبود علائم بالینی گوساله های تحت درمان مشهود بود. بیان ژن دفنسین و CD4، اثرات تعدیل کنندگی این ویتامین را برای سیستم ایمنی تأیید می‌کند، اما بیان ژن کاتالیسیدین، احتمالاً وابسته به تجویز دوز های بیشتری از ویتامین D3 می باشد.
چکیده انگلیسی:
The outbreak of calf pneumonia in herds occurs due to different pathogens. Vitamin D3 displays a regulatory effect on different cells, especially its pro-differential biological function and stimulates antimicrobial peptides. In the present study, the effects of vitamin D3 on the expression of antimicrobial peptides in experimental pasteurellosis in calves were assessed. Ten Holstein calves (2-4 months old) were randomly divided into two groups. Prepared Pasteurella multocida (3×109 CFU/mL) was inoculated in the trachea of all calves and Vitamin D3 was injected only in the treatment group following confirmation of pneumonia. Blood samples and broncho-alveolar lavage fluids were obtained from both groups at different time intervals and the peripheral blood mononuclear cells were isolated to evaluate the antimicrobial peptides gene expression. The expression of CD4, Cathelicidin, and Defensins genes was measured in vitro conditions following the addition of 10-6, 10-7 and 10-8 molar of vitamin D3. Defensins and CD4 gene expressions revealed a significant difference in the two groups, at the 48, 72, 96, and 120 hours after the challenge time, while the Cathelicidin gene was not expressed in both experimental groups. Surprisingly, increased expression of Cathelicidin, Defensins, and CD4 was observed at a concentration of 10-6 M of vitamin D3. According to the results of this study, vitamin D3 had positive effects on the immune system which was observed as significant improvement in the clinical symptoms of treated calves. The expression of lung-related Defensins and CD4 in vivo and in vitro approved the immunomodulatory effects of vitamin D3 but the gene expression of Cathelicidin is probably related to prescribing higher doses of vitamin D3.
منابع و مأخذ:
Abed, A.H., El-Seedy, F.R., Hassan, H.M., Nabih, A.M., Khalifa, E., Salem, S.E., et al. (2020). Serotyping, genotyping and virulence gene characterization of Pasteurella multocida and Mannheimia haemolytica isolates recovered from pneumonic cattle calves in North Upper Egypt. Veterinary Science, 7(4): 174.
Afsal, K., Hatishankar, M., Banurekha, V.V., Meenakshi, N., Parthasarathy, R.T. and Selvaraj, P. (2014). Effect of 1, 25-dihydroxy vitamin D3 on cathelicidin expression in patients with and without cavitary tuberculosis. Tuberculosis, 94(6): 599-605.
Algammal, A.A.M., El-Sayed, M.E., Youssef, F.M., Saad, S.A., Elhaig, M.M., Batiha, G.E., et al. (2020). Prevalence, the antibiogram and the frequency of virulence genes of the most predominant bacterial pathogens incriminated in calf pneumonia. AMB Express, 10)99(: 118-126.
Alva-Murillo, N., Téllez-Pérez, A.D., Medina-Estrada, I., Alvarez-Aguilar, C., Ochoa-Zarzosa, A. and López-Meza, J.E. (2014). Modulation of the inflammatory response of bovine mammary epithelial cells by cholecalciferol (vitamin D) during Staphylococcus aureus internalization. Microbial Pathogenesis, 77(1): 24-30.
Asgharpour, P., Mokhber Dezfouli, M.R., Nadealian, M.G., Eftekhari, Z. and Nikbakht Borojeni, G.R. (2020). Effects of 1, 25-dihydroxy vitamin D3 on clinical symptoms, pro-inflammatory and inflammatory cytokines in calves with experimental pneumonia. Research in Veterinary Science, 132(5): 186-193.
Beisswenger, C. and Balsm R. (2005). Antimicrobial Peptides in Lung Inflammation. Chemical Immunology and Allergy, 86(6): 55-71.
Bikle, D.D. (2009). Vitamin D and immune function: understanding common pathways. Current Osteoporosis Reports, 7(2): 58-63.
Chirumbolo, S., Bjørklund, G., Sboarina, A. and Vella, A. (2017). The Role of Vitamin D in the Immune System as a Pro-survival Molecule. Clinical Therapeutics, 39(5): 894-916.
Constable, P.D., Hinchcliff, K.W., Done, S.H. and Grunberg, W. (2017). Veterinary Medicine: A textbook of the diseases of cattle, horses, sheep, pigs and goats. 11th ed., Elsevier Health Sciences, pp: 786-840, 1278-1314.
Dabo, S.M., Taylor, J.D. and Confer, A.W. (2008). Pasteurella multocida and bovine respiratory disease. Animal Health Research Reviews, 8(2): 129-150.
DeRosa, D., Mechor, G., Staats, J., Chengappa, M. and Shryock, T. (2000). Comparison of Pasteurella spp. simultaneously isolated from nasal and transtracheal swabs from cattle with clinical signs of bovine respiratory disease. Journal of Clinical Microbiology, 38(1): 327-32.
DiRosa, M., Malaguarnera, M., Nicoletti, F. and Malaguarena, L. (2011). Vitamin D3: a helpful immune-modulator. Immunology, 134(2): 123-139.
Geraert, D. (2006). The importance of mycoplasma bovis in bovine respiratory Disease. Tijdschr Diergeneskd, 131(4): 124-126.
Gibbs, A. (2001). Practical approach to the control of pneumonia in housed calves. In Practice, 23(1): 32-9.
Guillot, X., Semerano, L., Saidenberg-Kermanac’h, N., Falgarone, G. and Boissier, M.C. (2010). Vitamin D and inflammation. Joint Bone Spine, 77(6): 552–557.
Harder, J. and Schroder, J.M. (2007). Antimicrobial Peptides Role in Human Health and Disease. 1st ed., Springer International Publishing, pp: 25- 180.
Hayes, C.E., Hubler, S.L., Moore, J.R., Barta, L.E., Praska, C. and Nashold, F.E. (2015). Vitamin D Actions on CD4+ T Cells in Autoimmune Disease. Frontiers in Immunology, 6(4): 100-109.
Hazlett, L. and Minhao, W.U. (2011). Defensins in innate immunity. Cell and Tissue Research, 343(1): 175-188.
Hewison, M. (2011). Antibacterial effects of vitamin D. Nature Reviews Endocrinology, 7(6): 337–345.
Izadpanah, A. and Gallo, R.L. (2005). Antimicrobial peptides. Journal of the American Academy Dermatology, 52(3): 381-390.
Karimkhani, H., Zahraie salehi, T., Sadeghi zali, M.H., Karimkhani. M. and Lameyi. R. (2011). Isolation of pasteurella multocida from cows and buffaloes in Urmia's Slaughter House. Archives of Razi Institute, 66(1): 37-41.
Merriman, K.E., Kweh, M.F., Powell, J.L., Lippolis, J.D. and Nelson, C.D. (2015). Multiple b-defensin genes are upregulated by the vitamin D pathway in cattle. Journal of Steroid Biochemistry & Molecular Biology, 154(1): 120-129.
Mohammadi, G.R., Sharifi, K. and Sepahi, S. (2004). Comparison of the therapeutic effects of florfenicol Tilmicosin in enzootic calf bronchopneumonia. Journal of the Faculty of Veterinary Medicine University of Tehran, 59(3): 277-282.
Mohammadi, G.R., Ghazvini, K. and Panah, H.A. (2006). Antimicrobial susceptibility testing of Mannheimia haemolytica and Pasteurella multocida isolated from calves with dairy calf pneumonia. Archives of Razi Institute, 61(2): 91-96.
Mohammadi, G.R., Nazifi, S., Rezakhani, A. and Esmailnejad, Z. (2007). Effect of transportation stress on blood and bronchoalveolar lavage fluid components in calves. Comparative Clinical Pathology, 16(4): 85-95.
Mokhber Dezfouli, M.R., Dousti, M., Lotfollahzadeh, S., Eftekhari, Z. and Nikbakht Boroujeni, G.R. (2017). Detection of annexin I and annexin II in serum of calves affected by experimental pneumonia with Pasteurella multocida. Journal of Veterinary Research, 72(2): 261-268.
Ozkanlar, Y., Aktas, M.S., Kaynar, O., Ozkanlar, S., Kirecci, E. and Yildiz, Y. (2012). Bovine respiratory disease in naturally infected calves: clinical signs, blood gases and cytokine response. Revue de Medicine Veterinaire, 163(3): 123-130.
Pincikova, T., Paquin‐Proulx, D., Sandberg, J.K., Flodström‐Tullberg, M. and Hjelte, M. (2007). Vitamin D treatment modulates immune activation in cystic fibrosis. Clinical & Experimental Immunology, 189(3): 359-371.
Reddy, K.V.R., Yedery, R.D. and Aranha, C. (2004). Antimicrobial peptides: premises and promises. International Journal of Antimicrobial Agents, 24(6): 536-547.
Rezaie Saber, A.P. (2014). Isolation of different bacteria from pneumonic lungs of cows slaughtered in Tabriz (IRAN) abattoir. Journal of Veterinary Clinical Phatology, 8(2): 481-491. [In Persian]
Selvaraj, P., Prabhu Anand, S., Harishnkar, M. and Alagarasu, K. (2009). Plasma 1,25 dihydroxy vitamin D3 level and expression of vitamin D receptor and Cathelicidin in pulmonary tuberculosis. Journal of Clinical Immunology, 29(4): 470-478.
Shayegh, J., Monadi, A.R. and Dolgari Sharaf, J. (2014). Molecular diversity of Pasteurella multocida isolated from cattle and buffaloes in Eaxt Azerbaijan province based on restriction endonuclease analysis. Journal of Veterinary Clinical Phatology, 8(1): 367-372. [In Persian]
Smith, B.P. (2015). Large Animal Internal Medicine. 5th edition. Elsevier Health Sciences. pp: 680-745.
Tecle, T., Tripathi, S.H. and Hartshorn, K.L. (2010). Defensins and cathelicidins in lung immunity. Innate Immunity, 16(3): 151-159.
White, J.H. (2010). Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. Journal of Steroid Biochemistry Molecular Biology, 121(1-2): 234-238.
_||_Abed, A.H., El-Seedy, F.R., Hassan, H.M., Nabih, A.M., Khalifa, E., Salem, S.E., et al. (2020). Serotyping, genotyping and virulence gene characterization of Pasteurella multocida and Mannheimia haemolytica isolates recovered from pneumonic cattle calves in North Upper Egypt. Veterinary Science, 7(4): 174.
Afsal, K., Hatishankar, M., Banurekha, V.V., Meenakshi, N., Parthasarathy, R.T. and Selvaraj, P. (2014). Effect of 1, 25-dihydroxy vitamin D3 on cathelicidin expression in patients with and without cavitary tuberculosis. Tuberculosis, 94(6): 599-605.
Algammal, A.A.M., El-Sayed, M.E., Youssef, F.M., Saad, S.A., Elhaig, M.M., Batiha, G.E., et al. (2020). Prevalence, the antibiogram and the frequency of virulence genes of the most predominant bacterial pathogens incriminated in calf pneumonia. AMB Express, 10)99(: 118-126.
Alva-Murillo, N., Téllez-Pérez, A.D., Medina-Estrada, I., Alvarez-Aguilar, C., Ochoa-Zarzosa, A. and López-Meza, J.E. (2014). Modulation of the inflammatory response of bovine mammary epithelial cells by cholecalciferol (vitamin D) during Staphylococcus aureus internalization. Microbial Pathogenesis, 77(1): 24-30.
Asgharpour, P., Mokhber Dezfouli, M.R., Nadealian, M.G., Eftekhari, Z. and Nikbakht Borojeni, G.R. (2020). Effects of 1, 25-dihydroxy vitamin D3 on clinical symptoms, pro-inflammatory and inflammatory cytokines in calves with experimental pneumonia. Research in Veterinary Science, 132(5): 186-193.
Beisswenger, C. and Balsm R. (2005). Antimicrobial Peptides in Lung Inflammation. Chemical Immunology and Allergy, 86(6): 55-71.
Bikle, D.D. (2009). Vitamin D and immune function: understanding common pathways. Current Osteoporosis Reports, 7(2): 58-63.
Chirumbolo, S., Bjørklund, G., Sboarina, A. and Vella, A. (2017). The Role of Vitamin D in the Immune System as a Pro-survival Molecule. Clinical Therapeutics, 39(5): 894-916.
Constable, P.D., Hinchcliff, K.W., Done, S.H. and Grunberg, W. (2017). Veterinary Medicine: A textbook of the diseases of cattle, horses, sheep, pigs and goats. 11th ed., Elsevier Health Sciences, pp: 786-840, 1278-1314.
Dabo, S.M., Taylor, J.D. and Confer, A.W. (2008). Pasteurella multocida and bovine respiratory disease. Animal Health Research Reviews, 8(2): 129-150.
DeRosa, D., Mechor, G., Staats, J., Chengappa, M. and Shryock, T. (2000). Comparison of Pasteurella spp. simultaneously isolated from nasal and transtracheal swabs from cattle with clinical signs of bovine respiratory disease. Journal of Clinical Microbiology, 38(1): 327-32.
DiRosa, M., Malaguarnera, M., Nicoletti, F. and Malaguarena, L. (2011). Vitamin D3: a helpful immune-modulator. Immunology, 134(2): 123-139.
Geraert, D. (2006). The importance of mycoplasma bovis in bovine respiratory Disease. Tijdschr Diergeneskd, 131(4): 124-126.
Gibbs, A. (2001). Practical approach to the control of pneumonia in housed calves. In Practice, 23(1): 32-9.
Guillot, X., Semerano, L., Saidenberg-Kermanac’h, N., Falgarone, G. and Boissier, M.C. (2010). Vitamin D and inflammation. Joint Bone Spine, 77(6): 552–557.
Harder, J. and Schroder, J.M. (2007). Antimicrobial Peptides Role in Human Health and Disease. 1st ed., Springer International Publishing, pp: 25- 180.
Hayes, C.E., Hubler, S.L., Moore, J.R., Barta, L.E., Praska, C. and Nashold, F.E. (2015). Vitamin D Actions on CD4+ T Cells in Autoimmune Disease. Frontiers in Immunology, 6(4): 100-109.
Hazlett, L. and Minhao, W.U. (2011). Defensins in innate immunity. Cell and Tissue Research, 343(1): 175-188.
Hewison, M. (2011). Antibacterial effects of vitamin D. Nature Reviews Endocrinology, 7(6): 337–345.
Izadpanah, A. and Gallo, R.L. (2005). Antimicrobial peptides. Journal of the American Academy Dermatology, 52(3): 381-390.
Karimkhani, H., Zahraie salehi, T., Sadeghi zali, M.H., Karimkhani. M. and Lameyi. R. (2011). Isolation of pasteurella multocida from cows and buffaloes in Urmia's Slaughter House. Archives of Razi Institute, 66(1): 37-41.
Merriman, K.E., Kweh, M.F., Powell, J.L., Lippolis, J.D. and Nelson, C.D. (2015). Multiple b-defensin genes are upregulated by the vitamin D pathway in cattle. Journal of Steroid Biochemistry & Molecular Biology, 154(1): 120-129.
Mohammadi, G.R., Sharifi, K. and Sepahi, S. (2004). Comparison of the therapeutic effects of florfenicol Tilmicosin in enzootic calf bronchopneumonia. Journal of the Faculty of Veterinary Medicine University of Tehran, 59(3): 277-282.
Mohammadi, G.R., Ghazvini, K. and Panah, H.A. (2006). Antimicrobial susceptibility testing of Mannheimia haemolytica and Pasteurella multocida isolated from calves with dairy calf pneumonia. Archives of Razi Institute, 61(2): 91-96.
Mohammadi, G.R., Nazifi, S., Rezakhani, A. and Esmailnejad, Z. (2007). Effect of transportation stress on blood and bronchoalveolar lavage fluid components in calves. Comparative Clinical Pathology, 16(4): 85-95.
Mokhber Dezfouli, M.R., Dousti, M., Lotfollahzadeh, S., Eftekhari, Z. and Nikbakht Boroujeni, G.R. (2017). Detection of annexin I and annexin II in serum of calves affected by experimental pneumonia with Pasteurella multocida. Journal of Veterinary Research, 72(2): 261-268.
Ozkanlar, Y., Aktas, M.S., Kaynar, O., Ozkanlar, S., Kirecci, E. and Yildiz, Y. (2012). Bovine respiratory disease in naturally infected calves: clinical signs, blood gases and cytokine response. Revue de Medicine Veterinaire, 163(3): 123-130.
Pincikova, T., Paquin‐Proulx, D., Sandberg, J.K., Flodström‐Tullberg, M. and Hjelte, M. (2007). Vitamin D treatment modulates immune activation in cystic fibrosis. Clinical & Experimental Immunology, 189(3): 359-371.
Reddy, K.V.R., Yedery, R.D. and Aranha, C. (2004). Antimicrobial peptides: premises and promises. International Journal of Antimicrobial Agents, 24(6): 536-547.
Rezaie Saber, A.P. (2014). Isolation of different bacteria from pneumonic lungs of cows slaughtered in Tabriz (IRAN) abattoir. Journal of Veterinary Clinical Phatology, 8(2): 481-491. [In Persian]
Selvaraj, P., Prabhu Anand, S., Harishnkar, M. and Alagarasu, K. (2009). Plasma 1,25 dihydroxy vitamin D3 level and expression of vitamin D receptor and Cathelicidin in pulmonary tuberculosis. Journal of Clinical Immunology, 29(4): 470-478.
Shayegh, J., Monadi, A.R. and Dolgari Sharaf, J. (2014). Molecular diversity of Pasteurella multocida isolated from cattle and buffaloes in Eaxt Azerbaijan province based on restriction endonuclease analysis. Journal of Veterinary Clinical Phatology, 8(1): 367-372. [In Persian]
Smith, B.P. (2015). Large Animal Internal Medicine. 5th edition. Elsevier Health Sciences. pp: 680-745.
Tecle, T., Tripathi, S.H. and Hartshorn, K.L. (2010). Defensins and cathelicidins in lung immunity. Innate Immunity, 16(3): 151-159.
White, J.H. (2010). Vitamin D as an inducer of cathelicidin antimicrobial peptide expression: past, present and future. Journal of Steroid Biochemistry Molecular Biology, 121(1-2): 234-238.
