analyzed the data; H.T.X. acute gastroenteritis that may be complicated by life-threatening systemic sequelae1. EHEC is usually a non-invasive pathogen2 that adheres to intestinal cells and forms attaching and effacing lesions3. Damage to ICA-110381 the intestinal epithelium allows bacterial virulence factors, such as Shiga toxin, to enter the systemic circulation4. Bacterial virulence factors circulate and bind to platelets, monocytes, and neutrophils as well as to platelet-monocyte and platelet-neutrophil complexes5,6. These factors can then be transferred to target organs, including the kidney and the brain4. Large amounts of circulating virulence factors can increase the risk of hemolytic uremic syndrome (HUS), in which red blood cells are destroyed and the kidney exhibits glomerular and tubular damage with extensive apoptosis of renal Rabbit Polyclonal to GFP tag cortical cells7,8. However, no specific treatment is available for EHEC-induced HUS. Treatment with antibiotics is not recommended because they may increase toxin release and cause complications9. Our previous studies showed that this expression of PR-39, one of host defense peptides (HDPs), was upregulated with ETEC challenge in two breeds of pigs10. HDPs are a group of gene encoded, cationic, small peptides that are essential effector molecules of the innate immune system11 existing ubiquitously in both herb and animal kingdoms12. Defensins and cathelicidins represent the two major classes of HDPs in vertebrates13,14,15. Thus far, 13 -defensins and 11 cathelicidins have been identified in pigs12. The 13 -defensins are porcine -defensin 1 (pBD1), pBD2, pBD3, pBD4, pBD104, pBD108, pBD114, pBD123, pBD125, pBD126, pBD129, epididymis protein 2 splicing variant C (pEP2C) and pEP2E12,16. The 11 porcine cathelicidins are proline-arginine-rich 39-amino-acid peptide (PR-39), proline-phenylalanine-rich prophenin-1 (PF-1) and PF-2, cysteine-rich PG 1 (PG-1) to PG-5, and ICA-110381 three porcine myeloid antimicrobial peptides (PMAP)-23, PMAP-36 and PMAP-3712. HDPs are produced constitutively by epithelial cells and phagocytes or are induced during inflammation and contamination at mucosal surfaces17,18,19. HDPs kill various microorganisms, including Gram-positive and Gram-negative bacteria, viruses, protozoa, and fungi12,20. HDPs also modulate the immune response by recruiting and promoting elements of the innate immune system21,22. Because of their antimicrobial and immune-regulatory functions, HDPs have been developed as promising drugs against antibiotic-resistant microbes20,21,23,24. Butyrate, a major species of short-chain fatty acid (SCFA) produced by bacterial fermentation of undigested carbohydrates in the colon25, is found to be capable of inducing HDP expression in human, rabbit, chicken, and various enterocytes16,26,27,28,29. Meanwhile, butyrate plays an important role in intestinalhealth24,29,43 and has been used to treat different inflammatory disease in clinical practice30,31,32,33. However, little is known about the mechanism of its anti-inflammatory activity. It is uncertain that if there are connections between the upregulation of HDP expression and the attenuated inflammatory levels after butyrate treatment. Here, an experiment in piglets treated with sodium butyrate (NaB) 2 days before O157:H7 challenge was designed to investigate porcine HDP expression in tissues, inflammation and O157:H7 load in feces. Furthermore, the mechanisms underlying butyrate-induced HDP gene expression were also examined. Results NaB alleviates clinical symptoms caused by O157:H7 contamination O157:H7-challenged piglets developed clinical indicators of disease, including loss of appetite, ruffled fur, decreased activity and lethargy, after 24?h of contamination. However, the piglets treated with NaB showed no symptoms. Body weight loss due to O157:H7 contamination in the NaB-treated group occurred before day 5, but animals began to recover by day 10 (Fig. 1A). Compared with the control group, ICA-110381 O157:H7-challenged piglets suffered from kidney enlargement (O157:H7 infections showed a normal kidney index and normal levels of hemoglobin, platelet counts and plasma creatinine concentrations. The microscopic analysis of piglet kidneys from the O157:H7-challenged group showed that glomeruli were shrunken and tubular epithelial cells were desquamated with common apoptotic features, such as cell shrinkage and membrane blebbing (Fig. 1G), whereas NaB treatment alleviated these histopathological indicators of kidney damage (Fig. 1H). No histopathological indicators were observed in either the control group (Fig. 1F) or the NaB group (Fig. 1I). Open in a separate window Physique 1 NaB alleviates clinical symptoms caused by O157:H7 inoculation.(A) Body weight is usually shown as a percentage of weight change from days 1 to 10. Pigs developed symptomatic diseases after inoculation with O157:H7. (B) Kidney index?=?kidney weight (g)/body weight (kg). (C) Hemoglobin (g/L), (D) platelet counts (/L), and (E) plasma creatinine levels were analyzed from precaval vein blood samples from the same pigs in (C) and (D). Data are presented as the mean??SEM. *Indicates a significant difference (O157:H7-challenged pig. (H) Renal cortex from a pig fed with.
