In a new paper, published this week in the online early edition of PNAS, researchers at the University of California, San Diego School of Medicine conclude that aspirin has a second effect: Not only does it kill cyclooxygenase, thus preventing production of the prostaglandins that cause inflammation and pain, it also prompts the enzyme to generate another compound that hastens the end of inflammation, returning the affected cells to homeostatic health. “Aspirin causes the cyclooxygenase to make a small amount of a related product called 15-HETE,” said senior author Edward A. Dennis, PhD, Distinguished Professor of Pharmacology, Chemistry and Biochemistry. “During infection and inflammation, the 15-HETE can be converted by a second enzyme into lipoxin, which is known to help reverse inflammation and cause its resolution – a good thing[1].”
Some study demonstrates that lipoxin affects both secretion and absorption in airway epithelium. In non‐CF bronchial epithelium, lipoxin increases ASL height by inhibiting ENaC to decrease Na+ absorption and by activating CFTR to enhance Cl‐secretion. In CF bronchial epithelium, lipoxin restores ASL height mainly by inhibiting ENaC in the absence of CFTR activity[2].
Inflammatory response has been a hot issue of biological research. There are IL-1, IL-2 and IL-17 signaling pathway in the inflammatory response, and among them, IL – 1 signaling pathway is particularly important. Interleukin-1 (IL-1) is a pro-inflammatory cytokine that signals primarily through the type 1 IL-1 receptor (IL-1R1). The activities of IL-1 include induction of fever, expression of vascular adhesion molecules, and roles in arthritis and septic shock. The inflammatory activities of IL-1 are partially derived by transcriptionally inducing expression of cytokines such as TNF-alpha and interferons, as well as inducing the expression of other inflammation-related genes. There are two forms of IL-1 encoded by distinct genes, IL-1 alpha and IL-1 beta. IL-1 beta is produced as a 269 amino acid precursor that is cleaved by IL-1beta converting enzyme (ICE) to the active IL-1 beta form that is secreted. IL-1 signaling is opposed by the naturally occurring peptide IL-1 receptor antagonist which is a therapeutic agent for the treatment of arthritis.The type 1 IL-1 receptor protein binds IL-1 beta but requires the IL-1 receptor accessory protein (IL-1RAcP) to transduce a signal. IL-1 binding cause’s activation of two kinases, IRAK-1 and IRAK-2, associated with the IL-1 receptor complex. IRAK-1 (IL-1 Receptor Associated Kinase) activates and recruits TRAF6 to the IL-1 receptor complex. TRAF6 activates two pathways, one leading to NF-kB activation and another leading to c-jun activation. The TRAF associated protein ECSIT leads to c-Jun activation through the Map kinase/JNK signaling system. TRAF6 also signals through the TAB1/TAK1 kinases to trigger the degradation of I-kB, and activation of NF-kB. The IL-1 signaling cascade represents a highly conserved response to pathogens through evolution, with homologs in insects and even in plants. The signal transduction cascade utilized by IL-1 receptor is similar to that of TNF, resulting in NF-kB activation, and is most similar to that of the Toll-like receptors that also participate in inflammatory signaling responses to pathogen components like endotoxin (see Toll-like receptor pathway)[3].
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References
[1] Norris PC, Gosselin D, Reichart D, Glass CK, Dennis EA. Proc Natl Acad Sci U S A. 2014 Aug 19. pii: 201404372.
[2] Al-Alawi M, Buchanan P, Verriere V, Higgins G, McCabe O, Costello RW, McNally P, Urbach V, Harvey BJ.Physiol Rep. 2014 Aug 7;2(8). pii: e12093. doi:10.14814/phy2.12093. Print 2014 Aug 1.
[3] http://www.bioon.com.cn/protocol/showarticle.asp?newsid=37270
