In human peripheral blood monocytes Interleukin-4 (IL4) and IL13 significantly upregulates the levels of proteins involved in inflammatory resolution including the cell surface protein CD36 (Berry et al. 2007).

The Platelet glycoprotein IV gene (CD36, PAS IV, GPIV) is transcribed to yield mRNA and the mRNA is translated to yield proteind.
The PPARG:RXRA heterodimer bound to fatty acids activates transcription of the Platelet glycoprotein IV (CD36, PAS IV, GPIV) gene. In mouse the Pparg:Rxra heterodimer binds the promoter of the Platelet glycoprotein IV gene (Lefterova et al. 2008).

CD36 (FAT) located in the plasma membrane of pancreatic beta cells transports fatty acids such as palmitate into the cell (Noushmehr et al. 2005).

Scavenger receptor CD36 has been reported to function as an essential co-receptor involved in recognition of LTA and certain diacylated lipoproteins and presenting them to the TLR2:TLR6 heterodimer at the cell surface. CD14, a GPI-anchored molecule found on the cell surface of human phagocytes, has been also implicated in TLR2:TLR6 signaling [Stuart L et al 2005; Hoebe KP et al 2005; Triantafilou M et al 2006; Nilsen NJ et al 2008]

TLR2 - in combination with TLR6 - plays a major role in recognizing lipoteichoic acid (LTA) and peptidoglycan wall products from Gram-positive bacteria, as well as Mycobacterial diacylated lipopeptides.

CD36 (Platelet glycoprotein IV) binds oxidized LDL (Janabi et al. 2000, Endemann et al. 1993) through both the lipid and the protein moieties of LDL (Boullier et al. 2000), oxidized phospholipids (Podrez et al. 2002), long-chain fatty acids (inferred from rat and mouse, Abumrad et al. 1993, Laugerette et al. 2005), hexarelin (a hexapeptide member of the growth hormone-releasing peptide family) (inferred from rat and mouse, Bodart et al. 2002), betaglucan (Means et al. 2009), oxidized and native phosphatidylserine (Greenberg et al. 2006) and apoptotic cells (Ren et al. 1995; Fadok et al. 1998), lipopeptide from Staphylococcus aureus as well as lipoteichoic acid from Gram-positive bacteria, both in cooperation with TLR2 (inferred from mouse, Hoebe et al. 2005). As inferred from mouse, CD36 also binds phosphatidylinositol, and HDL.

The Platelet glycoprotein IV (CD36):ligand complex is endocytosed (Zeng et al. 2003, McDermott_Roe et al. 2008, Nilsen et al. 2008, Collins et al. 2009). The endocytosis of CD36:oxidized LDL is independent of caveolin (Zeng et al. 2003) and dependent on actin (Collins et al. 2009). As inferred from mouse, endocytosis of CD36:oxidized LDL is independent of caveolae, microtubules, and actin cytoskeleton, but dependent on dynamin (Sun et al. 2007).

Oxidized low-density lipoprotein (oxLDL) and amyloid-beta sequestered by the scavenger receptor CD36 trigger sterile inflammatory signaling through a CD36:TLR4:TLR6 heteromerization (Stewart CR et al., 2010). The heterotrimeric CD36:TLR4:TLR6 signaling complex, acting via NFkappaB and reactive oxygen species, primes the NLRP3 inflammasome in response to oxLDL (Sheedy FJ et al., 2013).

CD14, a GPI-anchored molecule found on the cell surface of human phagocytes, has been identified as a co-receptor that interacts with LPS. CD14 has been also implicated in TLR-2 signalling [Hajishengallis G et al 2006; Zivkovic A et al 2011]. Studies have demonstrated that CD14 can bind to triacylated lipoproteins and mediate the activation of the innate immune system trough TLR2:TLR1 complex [Nakata T et al 2006; Manukyan M et al 2005; Triantafilou M et al 2006]

Dendritic cells (DCs) and macrophages recognize and phagocytose apoptotic cells/invading microorganisms using a variety of receptors including lectins, Mannose receptor (MR) (Stahl & Ezekowitz. 1998), CD36 (Savill 1997), CD14 (Devitt et al. 1998), scavenger receptor A (SR-A) (Platt et al. 1996) and integrin alphaVbeta5 (Savill et al. 1992, Savilli et al. 1990), then cross-present cell-associated antigens to CD8+ T cells. Ligands on apoptotic cell like sugars, phosphatidylserine and surface-bound thrombospondin (TSP) are recognized by these receptors and induce rearrangements in the actin cytoskeleton that lead to the internalization of the particle.

The SCARB1 (SR-BI, SR-BII):ligand complex is endocytosed (Calvo et al. 1997, Murao et al. 1997, Rhainds et al. 1999, Vishnyakova et al. 2003, Baranova et al. 2005, Eckhardt et al. 2004) but selective lipid uptake from lipoprotein particles does not require SR-BI endocytosis in mouse (Nieland et al. 2005) but is partly dependent on endocytosis in human (Zhang et al. 2007). HDL particles are resecreted after lipid unloading in the endocytic pathway (Pagler et al. 2006; Zhang et al. 2007). SR-BI colocalizes with caveolae (inferred from mouse, Babitt et al. 1997) while SR-BII, an alternatively spliced form of SCARB1, localizes to clathrin-coated pits due to a dileucine motif in the cytosolic tail (inferred from mouse, Eckhardt et al. 2006). Endocytosis of oxidized LDL by SR-BI is independent of caveolae, microtubules, and actin cytoskeleton (inferred from mouse, Sun et al. 2007).

SCARF1 (SREC-I) binds low density lipoprotein (LDL), oxidized LDL, acetylated LDL (Adachi et al. 1997), carbamylated LDL (Apostolov et al. 2009), beta glucan (Means et al. 2009), and calreticulin (Berwin et al. 2004). SREC-I binds Hsp90 and Hsp90-chaperoned peptides (Murshid et al. 2010) as well as Heat shock protein 110 (hsp110) and glucose-regulated protein (grp170) (inferred from mouse, Facciponte, Wang et al. 2007). SREC-I interacts with PorB of Neisseria gonorrhoeae and mediates host cell entry (Rechner et al. 2007).

SCARB1 (SR-BI) binds low density lipoprotein (LDL), acetylated LDL, oxidized LDL, high density lipoprotein (HDL) (Calvo et al. 1997, Murao et al. 1997, Rhainds et al. 1999, inferred from hamster in Acton et al. 1994). SCARB1 binds HDL via its protein moiety, including apolipoproteins A-I, A-II, CII, CIII and E (Bultel-Brienne et al. 2002, inferred from mouse in Xu, Laccotripe et al. 1997, Li et al. 2002). SCARB1 also binds serum amyloid A protein (Baranova et al. 2005), and lipopolysaccharide (LPS) (Vishnyakova et al. 2003). SCARB1 is expressed on the extracellular face of the plasma membrane of several types of polarized epithelial cells.

PPARG can be activated in cell cultures by adding ligands such as polyunsaturated fatty acids and certain prostanoids (prostaglandins). Endogenous fatty acids are relatively poor activators. Which ligands are most responsible for PPARG activation in the body has not yet been established. Generally, oxidized fatty acids such as 9(S')-hydroxyoctadeca-10,12-dienoic acid (9(S')-HODE) and 13(S')-HODE are more effective activators than are endogenous fatty acids. The thiazolidinedione (TZD) class of antidiabetic drugs are agonist ligands for PPARG (Lambe and Tugwood 1996).
FABP4 delivers ligands to PPARG directly. Binding of activator ligands to PPARG causes loss of corepressors such as SMRT/NCoR2, NCoR1, and HDAC3 and gain of interactions with the basal transcription machinery (Yoo et al. 2006). The TRAP220/MED1/DRIP205 subunit of the TRAP/Mediator (DRIP) complex binds directly to the LXXLL motif of PPARG and TRAP/Mediator is necessary for full transcriptional activation of target genes (Ge et al. 2008). PPARG also interacts with the MED14 subunit of the Mediator complex (Grontved et al. 2010).
Other coactivators, including NCOA1/SRC-1, NCOA2/TIF2/GRIP1, CBP, HAT/p300, and PRIP, interact with PPARG in a ligand-dependent way and enhance transcription (Gellman et al. 1999, Wallberg et al. 2003, Yang et al. 2000, Ge et al. 2002, Puigserver et al. 1999, Bugge et al. 2009, Steger et al. 2010).
The target genes of PPARG encode proteins involved in adipocyte differentiation (PGAR/ANGPTL4, PLIN, and aP2/FABP4), carbohydrate metabolism (PEPCK-C), and fatty acid transport (FAT/CD36, LPL).

Lipoteichoic acid (LTA) is a component of the cell wall of Gram-positive bacteria. LTA induces a toll-like receptor 2 (TLR2)-mediated inflammatory response upon initial binding to coreceptors CD36 and CD14 (Nilsen NJ et al. 2008).

High mobility group box protein 1 (HMGB1) is a ubiquitous nuclear protein that under normal conditions binds and bends DNA and facilitates gene transcription. In response to infection or injury, HMGB1 is actively secreted by innate immune cells and/or released passively by necrotic or damaged cells (Andersson U et al. 2000; Scaffidi P et al. 2002; Bonaldi T et al. 2003; Chen G et al. 2004; Beyer C et al. 2012; Yang H et al. 2013). Outside the cell, HMGB1 can serve as an alarmin to activate innate immune responses including chemotaxis and cytokine release in both normal and aberrant immunity (Andersson U et al. 2000; Zetterström CK et al. 2002; Voll RE et al. 2008; Harris HE et al. 2012; Diener KR et al. 2013; Yang H et al. 2013). HMGB1 has been implicated in TLR2-mediated inflammation (Yu M et al. 2006; Park JS et al. 2006). Addition of HMGB1 induced cellular activation and TLR2- and TLR4-mediated NFkappaB-dependent transcription in TLR2- or TLR4-transfected human embryonic kidney-293 (HEK293) cells (Park JS et al. 2006). Mouse Tlr2 was found to associate with immunoprecipitated Hmgb1 from mouse macrophage-like RAW264.7 cell lysates (Park JS et al. 2006). Anti-TLR2 antibodies dose-dependently attenuated HMGB1-induced IL-8 release in TLR2-expressing HEK293 cells and markedly reduced HMGB1 cell surface binding on murine macrophage-like RAW 264.7 cells (Yu M et al. 2006). Moreover, results of ELISA, surface plasmon resonance and native PAGE electrophoretic mobility shift analyses indicated that HMGB1 binds LTA in a concentration-dependent manner and that this binding is inhibited by LBP (Kwak MS et al. 2015). Native PAGE, fluorescence-based transfer and confocal imaging analyses indicated that HMGB1 catalytically disaggregated LTA transfering LTA to CD14. NFkappaB p65 nuclear transmigration, degradation of IkBalpha and reporter assay results demonstrated that NFkappaB activity in HEK293-hTLR2/6 cells was significantly upregulated by a mixture of LTA and soluble CD14 in the presence of HMGB1 (Kwak MS et al. 2015). Furthermore, the production of TNFalpha and IL6 in murine J774A.1 and RAW264.7 cells increased significantly following treatment with a mixture of LTA and HMGB1 compared with treatment with LTA or HMGB1 alone (Kwak MS et al. 2015). Thus, HMGB1 was proposed to play an important role in LTA-mediated inflammation by binding to LTA and transferring LTA to CD14, which is subsequently transferred to TLR2:TLR6 to induce an inflammatory response.