Laminar chemokine mRNA concentrations in horses with carbohydrate overload-induced laminitis.
Abstract: Chemokines play a vital role in leukocyte activation and emigration that reportedly plays a central role in laminar injury in equine laminitis. The purpose of this study was to evaluate the pattern of laminar chemokine expression in horses in the classical carbohydrate overload (CHO)-model of laminitis. Laminar samples were obtained 24h following water administration in the control group (CON, n=8), and at the onset of fever (≥ 102°F, 12-22 h post CHO, DEV group, n=8) and at the onset of lameness (20-48 h post CHO, LAM group, n=8) in induced horses. Real time quantitative PCR was performed on all samples in order to determine laminar mRNA concentrations of both CXC chemokines (CXCL1, CXCL6, CXCL8) and CC chemokines (CCL2 [MCP-1], CCL3 [MIP-1α], and CCL8 [MCP-2]). Data were subjected to ANOVA followed by Student-Newman-Keuls (P<0.05). Laminar mRNA concentrations for all CXC chemokines were increased (P<0.05) at both the DEV and LAM horses when compared to the control horses, whereas mRNA concentrations of CCL2 and CCL8 were only increased in the LAM horses when compared to controls and the DEV horses. When taken in context with our previous studies, CXCL1, CXCL6 and CXCL8 increases precede peak laminar leukocyte accumulation. Additionally, CCL2 and CCL8 expression corroborate previous reports of monocyte/macrophage accumulation in affected laminae. Compared with previous studies, our findings demonstrate that increased laminar CXC chemokine expression consistently precedes peak leukocyte accumulation and onset of lameness in CHO laminitis models. Chemokine antagonists may be considered as possible therapeutic targets to decrease the influx of leukocytes that occurs during the development of equine laminitis.
Published by Elsevier B.V.
Publication Date: 2011-07-28 PubMed ID: 21889804DOI: 10.1016/j.vetimm.2011.07.005Google Scholar: Lookup
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- Journal Article
- Research Support
- Non-U.S. Gov't
- Research Support
- U.S. Gov't
- Non-P.H.S.
Summary
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This study examined the role of chemokines, substances that trigger leukocyte activity, in horses suffering from laminitis induced by carbohydrate overload. It found that chemokine levels increase before peak leukocyte activity and this may be why lameness develops.
Research Purpose and Methodology
- The aim of this study was to investigate the pattern of laminar chemokine expression in horses suffering from carbohydrate overload (CHO)-induced laminitis. Laminitis is a painful and debilitating disease which commonly occurs in horses due to excess consumption of carbohydrates.
- For the experiment, laminar samples were taken from a control group of horses (CON) and from horses that were induced to laminitis (DEV and LAM groups).
- The samples were taken 24 hours after water was given to the CON group and at the onset of fever and lameness in the DEV and LAM groups.
- These samples were then subjected to a Real time quantitative PCR, a method used for measuring specific genetic material, to determine the concentration of various chemokines.
Results and Findings
- The study found that all CXC chemokines (CXCL1, CXCL6, CXCL8) were increased at both the DEV and LAM stages as compared to the control horses.
- In the case of the CC chemokines (CCL2 [MCP-1], CCL3 [MIP-1α], and CCL8 [MCP-2]), they were only increased in the LAM horses as compared to the controls and the DEV horses.
- This suggests that the increase in chemokines precedes the peak accumulation of leukocytes, white blood cells that play an essential role in the body’s immune response.
- The increased expression of CCL2 and CCL8 aligns with previous research, suggesting that monocyte/macrophage accumulation occurs in the affected laminae. Monocytes/macrophages are types of white blood cells involved in engulfing and digesting harmful organisms in the body.
Implications and Conclusion
- The study’s findings demonstrated that an increase in laminar CXC chemokine expression consistently occurs before peak leukocyte accumulation and the onset of lameness in horses suffering from CHO-induced laminitis.
- This suggests that chemokines function as a trigger for the excessive immune response seen in laminitis, potentially causing the painful symptoms seen in horses affected by the condition.
- Using chemokine antagonists, substances that inhibit the activity of chemokines, could therefore be a possible therapeutic target to reduce the influx of leukocytes during the development of laminitis, potentially reducing the severity of the disease in horses.
Cite This Article
APA
Faleiros RR, Leise BS, Watts M, Johnson PJ, Black SJ, Belknap JK.
(2011).
Laminar chemokine mRNA concentrations in horses with carbohydrate overload-induced laminitis.
Vet Immunol Immunopathol, 144(1-2), 45-51.
https://doi.org/10.1016/j.vetimm.2011.07.005 Publication
Researcher Affiliations
- Department of Veterinary Clinical Sciences, College of Veterinary Medicine, The Ohio State University, 440 VMAB, 1900 Coffey Rd., Columbus, OH 43210, USA.
MeSH Terms
- Animals
- Carbohydrate Metabolism
- Chemokine CCL2 / metabolism
- Chemokine CCL3 / metabolism
- Chemokine CCL8 / metabolism
- Chemokine CXCL1 / metabolism
- Chemokine CXCL6 / metabolism
- Chemokines / metabolism
- Foot Diseases / metabolism
- Foot Diseases / veterinary
- Hoof and Claw / chemistry
- Hoof and Claw / metabolism
- Horse Diseases / metabolism
- Horses
- Interleukin-8 / metabolism
- Lameness, Animal / metabolism
- RNA, Messenger / analysis
- Real-Time Polymerase Chain Reaction / veterinary
Citations
This article has been cited 5 times.- Burns TA, Watts MR, Belknap JK, van Eps AW. Digital lamellar inflammatory signaling in an experimental model of equine preferential weight bearing. J Vet Intern Med 2023 Mar;37(2):681-688.
- Cassimeris L, Engiles JB, Galantino-Homer H. Interleukin-17A pathway target genes are upregulated in Equus caballus supporting limb laminitis. PLoS One 2020;15(12):e0232920.
- Watts MR, Hegedus OC, Eades SC, Belknap JK, Burns TA. Association of sustained supraphysiologic hyperinsulinemia and inflammatory signaling within the digital lamellae in light-breed horses. J Vet Intern Med 2019 May;33(3):1483-1492.
- Dern K, van Eps A, Wittum T, Watts M, Pollitt C, Belknap J. Effect of Continuous Digital Hypothermia on Lamellar Inflammatory Signaling When Applied at a Clinically-Relevant Timepoint in the Oligofructose Laminitis Model. J Vet Intern Med 2018 Jan;32(1):450-458.
- Leise BS, Watts MR, Roy S, Yilmaz AS, Alder H, Belknap JK. Use of laser capture microdissection for the assessment of equine lamellar basal epithelial cell signalling in the early stages of laminitis. Equine Vet J 2015 Jul;47(4):478-88.
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