Diabetes alters the response to bacteria by enhancing fibroblast apoptosis.
Diabetics suffer from both more frequent bacterial infections and greater consequences of infection. However, bacteria-induced tissue destruction and the subsequent response in diabetics have received relatively little attention. To investigate this issue, we inoculated the scalp of control or db/db diabetic mice, with the pathogen Porphyromonas gingivalis, which causes connective tissue destruction in humans. Both bacteria-induced cytokine expression and tissue loss were similar in diabetic and control mice. However, there was a significantly higher rate of fibroblast-specific apoptosis in the diabetic group, which was measured as cells that were double positive for the terminal deoxynucleotidyltransferase-mediated deoxy-UTP nick end labeling assay and expression of vimentin. The higher rate of fibroblast apoptosis could be explained in the diabetic group by enhanced levels of activated caspase-3. Apoptosis was evident during the peak healing period and coincided with reduced numbers of fibroblasts, diminished collagen I and III expression, and significantly reduced formation of new connective tissue matrix in diabetic mice. Thus, diabetes may impair the healing response to bacteria-induced connective tissue loss by increasing the number of caspase-3-activated fibroblasts, leading to greater apoptosis and reduced numbers of fibroblastic cells.
Liu
Rongkun
R
Boston University School of Dental Medicine, W-202D, 700 Albany Street, Boston, Massachusetts 02118, USA.
Desta
Tesfahun
T
He
Hongbing
H
Graves
Dana T
DT
D000818:Animals; D017209:Apoptosis; D016866:Bacteroidaceae Infections / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D002452:Cell Count; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D005109:Extracellular Matrix / Q000378:metabolism; D005347:Fibroblasts / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D016966:Porphyromonas gingivalis; D012535:Scalp / Q000382:microbiology / Q000473:pathology; D018461:Soft Tissue Infections / Q000473:pathology