N9 microglial cells polarized by LPS and IL4 show differential responses to secondary environmental stimuli

Activation of murine microglial N9 cells is attenuated through cannabinoid receptor CB2 signaling

“…: no significance. microglial M1 and M2 states, such as iNOS, TNF-a, IL-1b and Arg-1, in the presence of stimulus [26,27]. Thus, we used N9 microglia to study microglial M1 and M2 states in this investigation.…”

Emerging roles of the γ-secretase-notch axis in inflammation

“…It has also been reported that γ-secretase-mediated Notch signaling determines polarization of macrophage and microglial cells by LPS. A γ-secretase inhibitor suppressed IL-12-producing M1 polarization, while IL-10-producing M2 polarization was promoted (Liu et al, 2012;Wang et al, 2010). It is also important to note that Notch signaling can be activated through a γ-secretaseindependent pathway based on a mutant form of Notch (Bush et al, 2001), suggesting a limitation of γ-secretase inhibitors to completely block the Notch signaling pathway.…”

“…γ-Secretase substrate γ-Secretase cleavage product Effects in inflammatory disease References Notch NICD ALPS and SLE increase lymphoproliferation, DNT, autoantibody production, and nephritis Teachey et al, 2008 Rheumatoid arthritis mediates TNF-α-induced IL-6 production; exacerbates RA symptoms; increases ICAM-1, NF-κB, proinflammatory cytokines, Th1 and Th17 cells, Th17 cell differentiation Jiao et al, 2012Park et al, 2013Jiao et al, 2014 Multiple sclerosis induces Th1 polarization by up-regulating Tbx21; regulates Th17 differentiation; increases Th17-associated cytokine secretion; cytosol localized NICD causes remyelination failure in OPCs in MS lesion Minter et al, 2005Keerthivasan et al, 2011Nakahara et al, 2009 Sepsis mediates the production of LPS-induced cytokines Tsao et al, 2011 Asthma increases Th2 cytokine levels by up-regulating GATA-3; decreases Th1 cytokine levels Kang et al, 2009 Systemic sclerosis exacerbates dermal fibrosis; increases profibrotic cytokines Dees et al, 2011 Behcet's disease increases Th17 response Qi et al, 2014 Ulcerative colitis enhances IL-22 induced STAT3 dependent transcription Murano et al, 2014 Ischemic stroke activates microglia cells; enhances leukocytes infiltration; promotes proliferation and differentiation of reactive astrocytes Arumugam et al, 2006Wei et al, 2011Park et al, 2013Cheng et al, 2014Marumo et al, 2013Shimada et al, 2011 Allergic airway inflammation induces IL-4 production, Th2 differentiation, airway hyperresponsiveness, and eosinophilic airway inflammation Okamoto et al, 2009 Atherosclerosis increases macrophage accumulation and activity in atherosclerotic lesion; attenuates the progression of atherosclerosis Aoyama et al, 2009 Calcific aortic stenosis enhances inflammatory response to TLR4 stimulation in human aortic valve interstitial cells through regulating NF-κB activation Zeng et al, 2012 Other inflammatory responses peripheral T cell activation and proliferation (canonical & noncanonical notch signaling); induces M1 polarization of LPS-stimulated macrophage and microglial cells; inhibits eosinophil differentiation Palaga et al, 2003Dongre et al, 2014Wang et al, 2010Liu et al, 2012Kang et ...…”

Exploring New Inflammatory Biomarkers and Pathways during LPS-Induced M1 Polarization

“…The alternative M2 phenotype that is related to the damage resolution [13] may include several subtypes [7] and is induced by IL-4, IL-10, and transforming growth factor- β (TGF- β ). Arginase 1 (arg1), found in inflammatory zone 1 (FIZZ1), and Ym1 are recognized markers of M2 polarization [14]. However, although the expression of these markers is used to differentiate microglia phenotypes, there is still much to learn about the determinants of microglia specific functional polarization.…”