Associate Professor King Khalid University King Khalid University, Asir, Saudi Arabia
Abstract: Abstract:
Background: Immunomodulatory protective effects of Mesenchymal stem cells (MSCs) are well established. Physiological activation of resident MSCs during a bacterial infection tends to protect the tissues by neutralizing the bacterial growth or spread. The exact mechanism is not clear however, it is speculated that the transcriptional activation of the pro-inflammatory cytokines and antimicrobial secretomes like reactive oxygen species (ROS) are the possible reason for its antibacterial activity. We currently investigated role of indigenous inflammatory cytokines augmenting ROS both secreted by activated MSCs which were in-turn activated though LPS signifying initial infection effecting subsequent inhibition of bacterial spread. Methodology: Umbilical cord blood MSCs were activated with low dose LPS (10ng/ml) for 12 hrs. The supernatant was collected post 24 hours for assessment of pro-inflammatory cytokine levels and ROS/RNS and other oxidants. The mRNA expression of the cytokines and tissue bound ROS were determined. The antibacterial studies were done by disc diffusion method using standard reference stains and clinical isolates of selected gram positive and negative bacteria.
Results: The results of the LPS activation showed 4 to 7 folds rise in pro-inflammatory cytokines TNF-, IL-, IL-6. We did not see significant rise of or IL-8 levels. The anti- bacterial evaluation by disc diffusion showed profound zone of clearance for certain stains of gram positive and negative bacteria in a concentration of cell homogenate dependent manner. The bacterial cells recovered post 6 hrs of disc diffusion showed raise in NADPH oxidase and ROS along with increased lipid peroxidation, DNA damage and carbonylation of proteins. Inference &
Conclusion: Pro-inflammatory cytokines are known to directly act on the bacterial cells. Further, like any other immune cells activated resident MSCs can eliminate bacteria like innate immune cells at the site of infection or in systemic circulation. In the current in-vitro observation, the increased secretion of the pro-inflammatory cytokines by MSCs have led to increased production of oxidants which in-turn directly killed bacterial cells.
Funding Source: King khalid university, Abha, Saudi Arabia
