Cytokine | Role of PR3 | Action of cytokine | References |
---|---|---|---|
Interleukin (IL)-1β | Proteolytically activates extracellular pro-forms to be cleaved into active counterparts by Caspase 1 in inflammasomes | • ↑ neutrophil activation and recruitment • canonical NFκB signalling • ↑ cyclooxygenases [44] and prostaglandin E production • pushes towards T helper cell (Th)17 differentiation | |
IL-18 | • Induces interferon (IFN)-γ and Fas ligand, ↑ differentiation to Th1, Th2 or Th17 responses (dependant on accompanying signals) | ||
Tumour necrosis factor (TNF)-α | Cleaves precursor to bioactive form (via two hypothesised cleavage sites at Ala15-Leu16 or Val77-Arg78) | • Activates the caspase and MEK cascades, and PI-3-kinase and canonical NFκB pathway • Activates Etk = ↑cellular adhesion, migration and propagation • ↑ neutrophil chemotaxis • Upregulation of pro-inflammatory genes e.g. IL-8, CCL2, CXCL10, COX-2, and pro-coagulants • Recruits apoptosis-inhibiting molecules • ↓ signalling by cIAP-mediated ubiquitination | |
IL-6 | Functionally inactivates and degrades the soluble IL-6 receptor (sIL-6R) – exact mechanisms unknown | • Disrupts trans-signalling activity • Prevents apoptosis • ↑ neutrophil recruitment and infiltration | |
IL-8 (CXCL8) | Truncates stored IL-8 (77) into the 10-fold more potent chemo-attractant IL-8 (70) through cleavage of an Ala-Lys bond | • ↑ respiratory burst • Potentiates inflammatory disease cycle • Drives neutrophil chemotaxis | [61] |
IL-17 (CTLA8) | Stimulation increases cytokine production | • Directs towards a dominant Th17 environment • T cell hypo-responsiveness | [62] |
IL-32 | Processes activating cytokines IL-1β, TNF-α and IFN-γ directly or indirectly; cleaves IL-32 at IL-32α to a more bioactive form | • Activates canonical NFκB and MAPK cascades • ↑ production of cytokines incl. TNF-α, IL-8 and CXCL2 production |