Date of Award

7-2010

Degree Type

Thesis

Degree Name

MS Biology

Department

Biology

Advisor

Heping Zhou

Committee Member

Angela Klaus

Committee Member

Tin-Chun Chu

Committee Member

Carroll Rawn

Committee Member

Carolyn Bentivegna

Keywords

Biology, Inflammatory mediators, LPS, Lipopolysaccharide

Abstract

Lipopolysaccharide (LPS) is the primary component of the outer membrane of Gram-negative bacteria and is responsible for the majority of inflammatory effects of infections from Gram-negative bacteria. To gain better understanding of the effects that postnatal age has on the inflammatory response, pups were randomly assigned to be treated with 250 µg/kg of LPS or saline at postnatal day (P) 1, P21, and P70. Two hours post stimulation, the pups were sacrificed and their livers were harvested for total RN A extraction. Relative mRNA levels of inflammatory genes and �-actin were determined using RT-PCR analysis with appropriate rat sense and antisense primers. The specific inflammatory mediators examined were toll-like receptor-4 (TLR4), cluster of differentiation 14 (CD14), myeloid differentiation factor 88 (Myd88), cytokines including interleukin (IL )-1 �. IL-6, and tumor necrosis factor (TNF)-a, and chemokines including macrophage inflammatory protein (MIP)-1 �, MIP-2, and monocyte chemotactic protein (MCP)-1. We found that the LPS-induced mRNA expression of the cytokines and chemokines examined appear to be increased as compared to the control pups. Furthermore, we showed that an activation of cytokines and chemokines in the liver exhibited age-dependency in pups treated with LPS at Pl, P21, and P70. The pattern shows an increase in relative mRNA expression of cytokines and chemokines as development progresses. Furthermore, we compared the kinetics of cytokine and chemokine induction in PI and P2 l animals. We found that that there was a delayed cytokine and chemokine induction at PI as compared to P2 l pups. Our data suggest that the hepatic innate immunity undergo significant development during early postnatal development, and the delayed inflammatory response in Pl animals may contribute to increased susceptibility of neonatal animals to infections.

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