Animal Bioscience

  • 제38권11호
  • /
  • Pages.2454-2463
  • /
  • 2025
  • /
  • 2765-0189(pISSN)
  • /
  • 2765-0235(eISSN)
아세아태평양축산학회 (Asian Australasian Association of Animal Production Societies)
권호 표지
DOI QR코드

DOI QR Code

Regulation of interleukin-1 beta gene expression and its function of defense mechanism in rumen epithelial cells from pre- and postweaning calves

  • Huseong Lee (Graduate School of Agricultural Science, Tohoku University) ;
  • Naoto Sugiyama (Graduate School of Agricultural Science, Tohoku University) ;
  • Koki Nishihara (Graduate School of Agricultural Science, Tohoku University) ;
  • Minji Kim (Graduate School of Agricultural Science, Tohoku University) ;
  • Satoshi Haga (Graduate School of Agricultural Science, Tohoku University) ;
  • Sanggun Roh (Graduate School of Agricultural Science, Tohoku University)
  • 투고 : 2025.01.20
  • 심사 : 2025.05.01
  • 발행 : 2025.11.01
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Objective: This study aimed to elucidate interleukin-1 beta (IL-1β) gene expression regulation and its function of defense mechanism in rumen epithelial cells of calves. Methods: Rumen tissues from six Holstein male calves were sampled at pre- (5 weeks of age, n = 3) and post-weaning (9 weeks of age, n = 3). IL-1β localization was analyzed using immunohistochemistry (IHC). Primary bovine rumen epithelial cells (BRECs) were treated with short-chain fatty acids (SCFAs), beta-hydroxybutyrate, lactic acid, lipopolysaccharide (LPS), and flagellin, and IL-1β gene expression was analyzed by quantitative real-time polymerase chain reaction. Additionally, bovine IL-1β-treated BRECs were assessed for cell proliferation, tight junction (TJ) protein expression, and chemokine mRNA expression. Results: IHC revealed IL-1β expression across all rumen epithelial layers. SCFAs, LPS, and flagellin significantly increased IL-1β mRNA expression (p<0.05). Regarding the gene expression of rumen TJ proteins, CLDN4 and OCLN in suckling and weaned calves, as well as ZO-1 in weaned calves, showed significant decreases (p<0.05), while CLDN1 in weaned calves showed a significant increase (p<0.05) in IL-1β-treated BRECs. Regarding the gene expression of chemokines, the CCL2 expression significantly decreased (p<0.05), while the CCL5 expression significantly increased (p<0.05) in both suckling and weaned IL-1β treated BRECs. IL-1β treatment enhanced cell proliferation (p<0.05). Conclusion: These results suggest that IL-1β induction by SCFAs, LPS, and flagellin, which increase in the rumen due to environmental changes, promotes cell proliferation in damaged rumen epithelium and contributes to its defense mechanism by upregulating CCL5 expression.

키워드

과제정보

This work was carried out with the support of JSPS KAKENHI (grant number: 23K18075) and "Cooperative research Program for Agriculture Science and Technology Development (Project No. RS-2023-00231889)" Rural Development Administration, Republic of Korea. This work was partly supported by JST (grant number: JPMJSP2114).

참고문헌

  1. Roh SG, Kuno M, Hishikawa D, et al. Identification of differentially expressed transcripts in bovine rumen and abomasum using a differential display method. J Anim Sci 2007;85:395-403. https://doi.org/10.2527/jas.2006-234
  2. Nickel R, Schummer A, Seiferle E, Sack WO. The viscera of the domestic mammals. Springer; 1979.
  3. Satoh H, Fukumori R, Kumano R, et al. Effects of starch content of calf starter on rumen properties and blood concentrations of metabolites and hormones in dairy calves under a high plane of milk feeding. Anim Sci J 2024;95: e13927. https://doi.org/10.1111/asj.13927
  4. Sakata T, Tamate H. Rumen epithelial cell proliferation accelerated by rapid increase in intraruminal butyrate. J Dairy Sci 1978;61:1109-13. https://doi.org/10.3168/jds.S0022-0302(78)83694-7
  5. Satoh H, Fukumori R, Osada T, Shimada K, Oikawa S, Isumi K. Effects of starch content of calf starter on feed intake, growth performance, and fecal properties in dairy calves under a high plane of milk replacer feeding. Anim Sci J 2023;94:e13911. https://doi.org/10.1111/asj.13911
  6. Agustinho BC, Mark AE, Laarman AH, Konetchy DE, Rezamand P. Effect of pH and lipopolysaccharide on tight junction regulators and inflammatory markers in intestinal cells as an experimental model of weaning transition in dairy calves. JDS Commun 2023;4:394-9. https://doi.org/10.3168/jdsc.2022-0333
  7. Kleen JL, Hooijer GA, Rehage J, Noordhuizen JPTM. Subacute ruminal acidosis (SARA): a review. J Vet Med A 2003;50:406-14. https://doi.org/10.1046/j.1439-0442.2003.00569.x
  8. Liu J, Xu T, Liu Y, Zhu W, Mao S. A high-grain diet causes massive disruption of ruminal epithelial tight junctions in goats. Am J Physiol Regul Integr Comp Physiol 2013; 305:R232-41. https://doi.org/10.1152/ajpregu.00068.2013
  9. Dinarello CA. Biologic basis for interleukin-1 in disease. Blood 1996;87:2095-147. https://doi.org/10.1182/blood.V87.6.2095.bloodjournal8762095
  10. Macleod T, Berekmeri A, Bridgewood C, Stacey M, McGonagle D, Wittman M. The immunological impact of IL-1 family cytokines on the epidermal barrier. Front Immunol 2021;12:808012. https://doi.org/10.3389/fimmu.2021.808012
  11. Hübner G, Brauchle M, Smola H, Madlener M, Fässler R, Werner S. Differential regulation of pro-inflammatory cytokines during wound healing in normal and glucocorticoidtreated mice. Cytokine 1996;8:548-56. https://doi.org/10.1006/cyto.1996.0074
  12. Barrientos S, Stojadinovic O, Golinko MS, Brem H, TomicCanic M. PERSPECTIVE ARTICLE: growth factors and cytokines in wound healing. Wound Repair Regen 2008; 16:585-601. https://doi.org/10.1111/j.1524-475X.2008.00410.x
  13. Stolte KN, Pelz C, Yapto CV, Raguse JD, Dommisch H, Danker K. IL-1β strengthens the physical barrier in gingival epithelial cells. Tissue Barriers 2020;8:1804249. https://doi.org/10.1080/21688370.2020.1804249
  14. Ning T, Shao J, Zhang X, et al. Ageing affects the proliferation and mineralization of rat dental pulp stem cells under inflammatory conditions. Int Endod J 2020;53:72-83. https://doi.org/10.1111/iej.13205
  15. Nakamura Y, Aihara R, Iwata H, Kuwayama T, Shirasuna K. IL1B triggers inflammatory cytokine production in bovine oviduct epithelial cells and induces neutrophil accumulation via CCL2. Am J Reprod Immunol 2021;85:e13365. https://doi.org/10.1111/aji.13365
  16. Nishihara K, Suzuki Y, Kim D, Roh S. Growth of rumen papillae in weaned calves is associated with lower expression of insulin-like growth factor-binding proteins 2, 3, and 6. Anim Sci J 2019;90:1287-92. https://doi.org/10.1111/asj.13270
  17. Nishihara K, Suzuki Y, Roh S. Ruminal epithelial insulin-like growth factor-binding proteins 2, 3, and 6 are associated with epithelial cell proliferation. Anim Sci J 2020;91:e13422. https://doi.org/10.1111/asj.13422
  18. Nishihara K, Suzuki Y, Haga S, Roh S. TLR5 ligand induces the gene expression of antimicrobial peptides and CXCL8 through IL-1β gene expression in cultured rumen epithelial cells. Anim Sci J 2024;95:e13972. https://doi.org/10.1111/asj.13972
  19. Vandesompele J, De Preter K, Pattyn F, et al. Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 2002;3:research0034.1. https://doi.org/10.1186/gb-2002-3-7-research0034
  20. Corrêa-Oliveira R, Fachi JL, Vieira A, Sato FT, Vinolo MAR. Regulation of immune cell function by short-chain fatty acids. Clin Transl Immunol 2016;5:e73. https://doi.org/10.1038/cti.2016.17
  21. Zhan K, Gong X, Chen Y, Jiang M, Yang T, Zhao G. Shortchain fatty acids regulate the immune responses via G protein-coupled receptor 41 in bovine rumen epithelial cells. Front Immunol 2019;10:2042. https://doi.org/10.3389/fimmu.2019.02042
  22. Nagaraja TG, Titgemeyer EC. Ruminal acidosis in beef cattle: the current microbiological and nutritional outlook. J Dairy Sci 2007;90:E17-38. https://doi.org/10.3168/jds.2006-478
  23. Dunlop RH, Hammond PB. D-lactic acidosis of ruminants. Ann N Y Acad Sci 1965;119:1109-32. https://doi.org/10.1111/j.1749-6632.1965.tb47466.x
  24. Anderson KL, Nagaraja TG, Morrill JL. Ruminal metabolic development in calves weaned conventionally or early. J Dairy Sci 1987;70:1000-5. https://doi.org/10.3168/jds.S0022-0302(87)80105-4
  25. Khafipour E, Krause DO, Plaizier JC. A grain-based subacute ruminal acidosis challenge causes translocation of lipopolysaccharide and triggers inflammation. J Dairy Sci 2009;92: 1060-70. https://doi.org/10.3168/jds.2008-1389
  26. Pan XH, Yang L, Beckers Y, et al. Thiamine supplementation facilitates thiamine transporter expression in the rumen epithelium and attenuates high-grain-induced inflammation in low-yielding dairy cows. J Dairy Sci 2017;100:5329-42. https://doi.org/10.3168/jds.2016-11966
  27. Jiang M, Wang K, Huang Y, et al. Quercetin alleviates lipopolysaccharide-induced cell oxidative stress and inflammatory responses via regulation of the TLR4-NF-κB signaling pathway in bovine rumen epithelial cells. Toxins 2023;15:512. https://doi.org/10.3390/toxins15080512
  28. Kent-Dennis C, Aschenbach JR, Griebel PJ, Penner GB. Effects of lipopolysaccharide exposure in primary bovine ruminal epithelial cells. J Dairy Sci 2020;103:9587-603. https://doi.org/10.3168/jds.2020-18652
  29. Garcia M, Bradford BJ, Nagaraja TG. INVITED REVIEW: ruminal microbes, microbial products, and systemic inflammation. Appl Anim Sci 2017;33:635-50. https://doi.org/10.15232/pas.2017-01663
  30. Hayashi F, Smith KD, Ozinsky A, et al. The innate immune response to bacterial flagellin is mediated by toll-like receptor 5. Nature 2001;410:1099-103. https://doi.org/10.1038/35074106
  31. Nishihara K, Kato D, Suzuki Y, et al. Comparative transcriptome analysis of rumen papillae in suckling and weaned Japanese Black calves using RNA sequencing. J Anim Sci 2018; 96:2226-37. https://doi.org/10.1093/jas/skx016
  32. Connor EE, Baldwin VI RL, Li C, Li RW, Chung H. Gene expression in bovine rumen epithelium during weaning identifies molecular regulators of rumen development and growth. Funct Integr Genomics 2013;13:133-42. https://doi.org/10.1007/s10142-012-0308-x
  33. Yamamoto T, Kojima T, Murata M, et al. IL-1β regulates expression of Cx32, occludin, and claudin-2 of rat hepatocytes via distinct signal transduction pathways. Exp Cell Res 2004;299:427-41. https://doi.org/10.1016/j.yexcr.2004.06.011
  34. Kobayashi K, Matsunaga K, Tsugami Y, Wakasa H, Nishimura T. IL-1β is a key inflammatory cytokine that weakens lactation-specific tight junctions of mammary epithelial cells. Exp Cell Res 2021;409:112938. https://doi.org/10.1016/j.yexcr.2021.112938
  35. Li S, Ma T, An Y, et al. The impact of different dietary ratios of soluble carbohydrate-to-neutral detergent fiber on rumen barrier function and inflammation in dumont lambs. Animals 2024;14:1666. https://doi.org/10.3390/ani14111666
  36. Yu ASL, McCarthy KM, Francis SA, et al. Knockdown of occludin expression leads to diverse phenotypic alterations in epithelial cells. Am J Physiol Cell Physiol 2005;288:C1231-41. https://doi.org/10.1152/ajpcell.00581.2004
  37. Phillips BE, Cancel L, Tarbell JM, Antonetti DA. Occludin independently regulates permeability under hydrostatic pressure and cell division in retinal pigment epithelial cells. Invest Ophthalmol Vis Sci 2008;49:2568-76. https://doi.org/10.1167/iovs.07-1204
  38. Kuo WT, Odenwald MA, Turner JR, Zuo L. Tight junction proteins occludin and ZO-1 as regulators of epithelial proliferation and survival. Ann N Y Acad Sci 2022;1514:21-33. https://doi.org/10.1111/nyas.14798
  39. Davis TME, Holdright DR, Schulenberg WE, Turner RC, Joplin GF. Retinal pigment epithelial change and partial lipodystrophy. Postgrad Med J 1988;64:871-4. https://doi.org/10.1136/pgmj.64.757.871
  40. Hunt RC, Fox A, al pakalnis V, et al. Cytokines cause cultured retinal pigment epithelial cells to secrete metalloproteinases and to contract collagen gels. Invest Ophthalmol Vis Sci 1993;34:3179-86.
  41. Poritz LS, Harris III LR, Kelly AA, Koltun WA. Increase in the tight junction protein claudin-1 in intestinal inflammation. Dig Dis Sci 2011;56:2802-9. https://doi.org/10.1007/s10620-011-1688-9
  42. Oshima T, Koseki J, Chen X, Matsumoto T, Miwa H. Acid modulates the squamous epithelial barrier function by modulating the localization of claudins in the superficial layers. Lab Invest 2012;92:22-31. https://doi.org/10.1038/labinvest.2011.139
  43. Thomas LH, Wickremasinghe MIY, Friedland JS. IL-1β stimulates divergent upper and lower airway epithelial cell CCL5 secretion. Clin Immunol 2007;122:229-38. https://doi.org/10.1016/j.clim.2006.10.004
  44. Hussen J, Frank C, Düvel A, Koy M, Schuberth HJ. The chemokine CCL5 induces selective migration of bovine classical monocytes and drives their differentiation into LPShyporesponsive macrophages in vitro. Dev Comp Immunol 2014;47:169-77. https://doi.org/10.1016/j.dci.2014.07.014
  45. Hume DA, Ross IL, Himes SR, Tedjo Sasmono R, Wells CA, Ravasi T. The mononuclear phagocyte system revisited. J Leukoc Biol 2002;72:621-7. https://doi.org/10.1189/jlb.72.4.621