TY - JOUR
T1 - Inflammatory responses to induced infectious endometritis in mares resistant or susceptible to persistent endometritis
AU - Christoffersen, Mette
AU - Woodward, Elizabeth
AU - Bojesen, Anders Miki
AU - Jacobsen, Stine
AU - Petersen, Morten Rønn
AU - Troedsson, Mats H. T.
AU - Lehn-Jensen, Henrik
PY - 2012/3/29
Y1 - 2012/3/29
N2 - Background: The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine inoculation of 10 5 colony forming units (CFU) Escherichia coli in mares. Before inoculation, mares were classified as resistant or susceptible to persistent endometritis based on their uterine inflammatory response to infusion of 10 9 killed spermatozoa and histological assessment of the endometrial quality. Endometrial biopsies were obtained 3, 12, 24 and 72 hours (h) after bacterial inoculation and blood samples were obtained during the 7 day period post bacterial inoculation. Expression levels of cytokines and SAA were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR).Results: Compared to levels in a control biopsy (obtained in the subsequent estrous), resistant mares showed an up-regulation of IL-1β, IL-6, IL-8 and TNF-α at 3 h after E. coli inoculation, while susceptible mares showed increased gene expression of IL-6 and IL-1ra. Susceptible mares had a significant lower gene expression of TNF-α,IL-6 and increased expression of IL-1ra 3 h after E. coli inoculation compared to resistant mares. Susceptible mares showed a sustained and prolonged inflammatory response with increased gene expression levels of IL-1β, IL-8, IL-1ra and IL-1β:IL-1ra ratio throughout the entire study period (72 h), whereas levels in resistant mares returned to estrous control levels by 12 hours. Endometrial mRNA transcripts of IL-1β and IL-1ra were significantly higher in mares with heavy uterine bacterial growth compared to mares with no/mild growth.All blood parameters were unaffected by intrauterine E. coli infusion, except for a lower gene expression of IL-10 at 168 h and an increased expression of IL-1ra at 48 h observed in susceptible mares compared to resistant mares.Conclusions: The current investigation suggests that endometrial mRNA transcripts of pro-inflammatory cytokines in response to endometritis are finely regulated in resistant mares, with initial high expression levels followed by normalization within a short period of time. Susceptible mares had a prolonged expression of pro-inflammatory cytokines, supporting the hypothesis that an unbalanced endometrial gene expression of inflammatory cytokines might play an important role in the pathogenesis of persistent endometritis.
AB - Background: The objective of the study was to evaluate the gene expression of inflammatory cytokines (interleukin [IL]-1β, IL-6, IL-8, IL-10, tumor necrosis factor [TNF]-α, IL-1 receptor antagonist [ra] and serum amyloid A (SAA) in endometrial tissue and circulating leukocytes in response to uterine inoculation of 10 5 colony forming units (CFU) Escherichia coli in mares. Before inoculation, mares were classified as resistant or susceptible to persistent endometritis based on their uterine inflammatory response to infusion of 10 9 killed spermatozoa and histological assessment of the endometrial quality. Endometrial biopsies were obtained 3, 12, 24 and 72 hours (h) after bacterial inoculation and blood samples were obtained during the 7 day period post bacterial inoculation. Expression levels of cytokines and SAA were determined by quantitative real-time reverse transcriptase PCR (qRT-PCR).Results: Compared to levels in a control biopsy (obtained in the subsequent estrous), resistant mares showed an up-regulation of IL-1β, IL-6, IL-8 and TNF-α at 3 h after E. coli inoculation, while susceptible mares showed increased gene expression of IL-6 and IL-1ra. Susceptible mares had a significant lower gene expression of TNF-α,IL-6 and increased expression of IL-1ra 3 h after E. coli inoculation compared to resistant mares. Susceptible mares showed a sustained and prolonged inflammatory response with increased gene expression levels of IL-1β, IL-8, IL-1ra and IL-1β:IL-1ra ratio throughout the entire study period (72 h), whereas levels in resistant mares returned to estrous control levels by 12 hours. Endometrial mRNA transcripts of IL-1β and IL-1ra were significantly higher in mares with heavy uterine bacterial growth compared to mares with no/mild growth.All blood parameters were unaffected by intrauterine E. coli infusion, except for a lower gene expression of IL-10 at 168 h and an increased expression of IL-1ra at 48 h observed in susceptible mares compared to resistant mares.Conclusions: The current investigation suggests that endometrial mRNA transcripts of pro-inflammatory cytokines in response to endometritis are finely regulated in resistant mares, with initial high expression levels followed by normalization within a short period of time. Susceptible mares had a prolonged expression of pro-inflammatory cytokines, supporting the hypothesis that an unbalanced endometrial gene expression of inflammatory cytokines might play an important role in the pathogenesis of persistent endometritis.
KW - Animals
KW - Biopsy
KW - Cytokines
KW - Endometritis
KW - Female
KW - Gene Expression Profiling
KW - Gene Expression Regulation
KW - Horse Diseases
KW - Horses
KW - Inflammation
KW - Least-Squares Analysis
KW - RNA, Messenger
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Infectious endometritis,
KW - Susceptibility
KW - Cytokines
KW - Serum amyloid A
U2 - 10.1186/1746-6148-8-41
DO - 10.1186/1746-6148-8-41
M3 - Journal article
C2 - 22458733
SN - 1746-6148
VL - 8
JO - B M C Veterinary Research
JF - B M C Veterinary Research
IS - 41
ER -