Master of Science (MS)
First Committee Member
Katherine M. Howard
Second Committee Member
Ronald K. Gary
Number of Pages
Inflammation is a highly complex and beneficial response of the host innate immune system often characterized by redness or swelling of the infected area as a result of an injurious stimulus. The principal purpose of the inflammatory response is to rid the infected area of the noxious stimulus and hasten host recovery. Though the inflammatory response is both necessary and beneficial, if left unregulated, it can exact a devastating toll on the host. Thus, an understanding of the various mediators that are able to evoke an inflammatory response and the signaling of these mediators is crucial. One such mediator, central in initiating an inflammatory response, is the biologically active phospholipid platelet-activating factor (PAF, 1-O-alkyl-2-acetyl- sn-glycero-3-phosphocholine). This phospholipid is converted to its biologically inactive form by a calcium-independent phospholipase A2 called PAF acetylhydrolase (PAF-AH). Thus, the action of PAF-AH provides a mechanism by which to hinder the propagation of an inflammatory response. In this study, the proinflammatory mediators, lipopolysaccharide (LPS), PAF, and tumor necrosis factor-alpha (TNF-alpha) were investigated for their ability to upregulate PAF-AH expression. The cellular signaling pathways activated by these mediators were also investigated. We have demonstrated the ability of LPS, PAF, and TNF-alpha to upregulate PAF-AH levels. Further, we showed that the LPS-induced upregulation of PAF-AH levels is partially p38MAPK-dependent. The remaining LPS-induced signaling is mediated through the PAF receptor. The TNF-alpha and PAF-induced upregulation of PAF-AH levels is not p38MAPK dependent and the PAF acetylhydrolase induction observed may be the result of increased PAF production or signaling through separate pathway(s). We further demonstrate the ability of reactive oxygen species to induce the expression PAF acetylhydrolase.
Acetylhydrolase; Activating; Activation; Factors; Mediators; Platelet; Proinflammatory
Biochemistry; Immunology; Biophysics
University of Nevada, Las Vegas
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Abdel-al, Mohammed, "Activation of platelet-activating factor acetylhydrolase by proinflammatory mediators" (2008). UNLV Retrospective Theses & Dissertations. 2334.