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. 2019 May 14;3(7):1302–1320. doi: 10.1210/js.2019-00053

Figure 2.

Figure 2.

Schematic of the proposed mechanisms by which norepinephrine (NE) and corticosterone/cortisol (CORT) regulate sterile inflammation. NE promotes inflammation by (i) facilitating glutamate (GLUT) release and production of ATP by astrocytes that then promote the oligomerization of the NLRP3 inflammasome; (ii) acting at β-ARs to induce IL-1β production through a cAMP/ERK-dependent pathway, which can lead to IL-1β acting in an autocrine fashion to induce NFκB signaling pathways and production of NLRP3, IL-6, TNF-α, and pro-IL-1β; and (iii) causing the release of HSP72, which acts at TLR 2/4 to stimulate NFκB signaling. CORT promotes inflammation by (i) causing the release of HMGB1, which activates TLR 2/4 signaling pathways and (ii) downregulating CD200R and CX3CR1, which are negative regulators of inflammatory responses in microglia. NE and CORT also have anti-inflammatory properties that include inhibiting NFκB signaling and upregulating IL-1RA, IL-1R2, IL-10, and IκBα. CORT also has the ability to suppress noradrenergic activity, thereby reducing NE release. ERK, extracellular signal-regulated kinase; IL-1R2, IL-1 receptor type 2; IκBα, nuclear factor of κ light polypeptide gene enhancer in β-cells inhibitor α; CD200R, CD200 receptor; CX3CR1, CX3C receptor type 1.