inflammation Flashcards
inflammatory mechanisms
How does IL-1 stimulate prostaglandin release?
IL-1 sensitizes cells to bradykinin by upregulating bradykinin receptors, which then induce prostanoid release. Bradykinin is a peptide (C50H73N15O11) that causes blood vessels to dilate due to release of prostacyclin, nitric oxide, and endothelium-derived hyperpolarizing factor.
How does apolipoprotein L1 account for resistance to infection as well as chronic renal disease in West Africans?
APOL1 gene codes for Apolipoprotein L1 which occurs only in African primates with a BH3 domain associated with programmed cell death and a PFD domain (pore forming). The protein accounts for West African resistance to trypanosomiasis wherein parasite lysosomes become excessively permeable to chloride and burst. It also accounts for focal glomerular sclerosis which is increased in blacks and HIV infection.
What proteins make up the cytoplasmic NFkB complex?
Cytoplasmic NFkB consists of a heterodimer p50 and Rel held together by IkB
Many types of granules are found within polymorphonuclear leukocytes?
Granule membrane contains receptors and signal proteins. Neutrophil granules are 3 types: 1) azurophilic granules containing microbiocidal proteins, acid hydrolases, serine proteases (PR3, myeloperoxidase). 2) specific granules-lactoferrin, matrix contains hydrolyzes distinct from azurophilic granules, vitamin B12 binding protein, cytochrome component of phagocytic NADPH oxidase, other chemotactic, obsonic, and adhesion protein receptors. 3) tertiary granules: cathepsin and gelatinase
What transcription factors are generated by Toll and IL-1 receptors?
TIR (Toll IL-1) domain is on signaling IL-1 receptor and Toll-like receptors which then begins signaling pathways that generate NF-kB, JNKs, ERKs, and mAPKs transcription factors.
What pathways are stimulated after IL-1 receptor activation?
IL-1 stimulates the transmembrane receptor IL-1R, which has many associated proteins including ACCP1, MyD88, IRAK and TRAF6. MyD88, IRAK and TRAF6 also associate with Toll like receptors. These complexes stimulate NIK which then phosphorylates IkB-alpha which is then ubiquinated and destroyed releasing p65 (RelA) and p50 (NF-kB1), transcription factors for inflammatory response-TNFα, INF.
What is angiopoietin-like protein 2?
Angiopoietin-like 2 (ANGPTL2) is 493-amino acid containing the coil-coiled and fibrinogen-like domains conserved in angiopoietins. It binds weakly to angiopoietin receptors and functions as an inflammatory mediator increasing NF-kB production. It is increased in keratinocytes in dermatomyositis.
How do glucocorticoids inhibit the prostaglandin pathway?
Glucocorticoids increase expression of annexin 1 (lipocortin) which inhibits phospholipase A2 thus preventing arachadonic acid from becoming metabolized to prostaglandins. Annexins bind cell membrane phospholipids in a calcium dependent manner. They are important in determining cell shape as well as the processes of vesicle formation, exocytosis and endocytosis, and calcium channel formation.
