Activating signals and intracellular pathways of myeloid-derived cells. (A) Signaling pathways upon inflammatory activation of macrophages. Saturated fatty acids (SFA) and pathogen-associated-molecular-patterns (PAMPs) as well as danger-associated-molecular-patterns (DAMPs) activate the transcription factors NF-κB and activator protein 1 (AP-1), ultimately leading to the transcription of inflammatory and glycolytic genes. Further, activation of the inflammasome through multiple activating signals results in enhanced production of inflammatory cytokines (e.g., IL-1β, IL-18) via caspase-1. (B) Anti-inflammatory signaling pathways in macrophages. Anti-inflammatory cytokines (e.g., IL-4, IL-13) as well as polyunsaturated fatty acids (PUFA) and RORα lead to the transcription of PPARs and KLF4, respectively, enhancing the transcription of anti-inflammatory and metabolic genes. Moreover, inhibition of NF-κB is induced through PUFA, low density lipoprotein (LDL) and adiponectin, thereby impeding the transcription of inflammatory associated genes. AMP, adenosine monophosphate; AMPK, AMP-activated protein kinase; ASC, apoptosis-associated speck like protein containing a caspase recruitment domain; ATP, adenosine triphosphate; IKK, inhibitory κB kinase; LXR, liver X receptor; MAPK, mitogen-activated protein kinase; ROS, reactive oxygen species.