SOCS Proteins in Macrophage Polarization and Function

Wilson, Heather M.

doi:10.3389/fimmu.2014.00357

Cited by 140 publications

(134 citation statements)

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“…However, O 2 -PS40-cultured cells also expressed significantly more SOCS1 (Wilson, 2014;Whyte et al, 2011) than PS-cultured cells. SOCS1 is associated with M2 macrophage activation as it downregulates IFN-␥-driven JAK2/STAT1 and TLR/NF-B signalling, and promotes arginase 1 expression (Wilson, 2014). Interestingly, Whyte et al reported that SOCS1 can also inhibit IL-10 secretion (Whyte et al, 2011).…”

Section: Discussionmentioning

confidence: 91%

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The impact of surface chemistry modification on macrophage polarisation

et al. 2016

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Macrophages are innate immune cells that have a central role in combating infection and maintaining tissue homeostasis. They exhibit remarkable plasticity in response to environmental cues. At either end of a broad activation spectrum are pro-inflammatory (M1) and anti-inflammatory (M2) macrophages with distinct functional and phenotypical characteristics. Macrophages also play a crucial role in orchestrating immune responses to biomaterials used in the fabrication of implantable devices and drug delivery systems. To assess the impact of different surface chemistries on macrophage polarisation, human monocytes were cultured for 6 days on untreated hydrophobic polystyrene (PS) and hydrophilic O2 plasma-etched polystyrene (O2-PS40) surfaces. Our data clearly show that monocytes cultured on the hydrophilic O2-PS40 surface are polarised towards an M1-like phenotype, as evidenced by significantly higher expression of the pro-inflammatory transcription factors STAT1 and IRF5. By comparison, monocytes cultured on the hydrophobic PS surface exhibited an M2-like phenotype with high expression of mannose receptor (MR) and production of the anti-inflammatory cytokines IL-10 and CCL18. While the molecular basis of such different patterns of cell differentiation is yet to be fully elucidated, we hypothesise that it is due to the adsorption of different biomolecules on these surface chemistries. Indeed our surface characterisation data show quantitative and qualitative differences between the protein layers on the O2-PS40 surface compared to PS surface which could be responsible for the observed differential macrophage polarisation on each surface.

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Section: Discussionmentioning

confidence: 91%

“…33A). Given that the balance of SOCS1 and SOCS3 expression in macrophages affects their activation state (Wilson, 2014), our data suggest that macrophages cultured on polystyrene display a unique phenotype that may be directed towards a more pro-inflammatory or anti-inflammatory state by modifications to surface wettability.…”

Section: Discussionmentioning

confidence: 97%

The impact of surface chemistry modification on macrophage polarisation

et al. 2016

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“…However, incubation of AECs with the conditioned media from LPS-activated RAW 264.7 cells triggered the production in Il10 , Tgfb and Il6 in AECs. These molecules are known M2 activators that signal through different pathways involving specific receptors [41]. Usually working as an inflammatory cytokine, IL6 can also have anti-inflammatory and pro-regenerative properties when it activates the classical signaling pathway (through both gp130 and IL6 receptor), compared to the trans-signaling mediated by the soluble form of IL6 receptor [42].…”

Section: Discussionmentioning

confidence: 99%

Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence

et al. 2016

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Amniotic epithelial cells (AECs) are a class of fetal stem cells that derives from the epiblast and resides in the amnion until birth. AECs are suitable candidates for regenerative medicine because of the ease of collection, their low immunogenicity and inability to form tumors after transplantation. Even though human AECs have been widely investigated, the fact remains that very little is known about AECs isolated from rat, one of the most common animal models in medical testing. In this study, we showed that rat AECs retained stemness properties and plasticity, expressed the pluripotency markers Sox2, Nanog, and Oct4 and were able to differentiate toward the osteogenic lineage. The addition of conditioned medium collected from rat AECs to lipopolysaccharide-activated macrophages elicited anti-inflammatory properties through a decrease of Tnfa expression and slowed tumor cell proliferation in vitro and in vivo. The senescence-associated secretory phenotype was also significantly lower upon incubation of senescent human IMR-90 fibroblast cells with conditioned medium from rat AECs. These results confirm the potential of AECs in the modulation of inflammatory mechanisms and open new therapeutic possibilities for regenerative medicine and anti-aging therapies as well.

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“…Expression of SOCS proteins is tightly regulated (52,53), and detection of endogenous SOCS proteins has proven to be exceptionally difficult (54). To detect endogenous SOCS1, U937 human monocytes were treated with 26S proteosome inhibitor, MG-132, at the time of IL-4 stimulation to allow for SOCS protein detection.…”

Section: Kinetics Of Irs-2 Tyrosine Phosphorylation In Response Tomentioning

confidence: 99%

Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome

McCormick¹,

Gowda²,

Fang³

et al. 2016

Journal of Biological Chemistry

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Allergic asthma is a chronic lung disease initiated and driven by Th2 cytokines IL-4/-13. In macrophages, IL-4/-13 bind IL-4 receptors, which signal through insulin receptor substrate (IRS)-2, inducing M2 macrophage differentiation. M2 macrophages correlate with disease severity and poor lung function, although the mechanisms that regulate M2 polarization are not understood. Following IL-4 exposure, suppressor of cytokine signaling (SOCS)1 is highly induced in human monocytes. We found that siRNA knockdown of SOCS1 prolonged IRS-2 tyrosine phosphorylation and enhanced M2 differentiation, although siRNA knockdown of SOCS3 did not affect either. By co-immunoprecipitation, we found that SOCS1 complexes with IRS-2 at baseline, and this association increased after IL-4 stimulation. Because SOCS1 is an E3 ubiquitin ligase, we examined the effect of proteasome inhibitors on IL-4-induced IRS-2 phosphorylation. Proteasomal inhibition prolonged IRS-2 tyrosine phosphorylation, increased ubiquitination of IRS-2, and enhanced M2 gene expression. siRNA knockdown of SOCS1 inhibited ubiquitin accumulation on IRS-2, although siRNA knockdown of SOCS3 had no effect on ubiquitination of IRS-2. Monocytes from healthy and allergic individuals revealed that SOCS1 is induced by IL-4 in healthy monocytes but not allergic cells, whereas SOCS3 is highly induced in allergic monocytes. Healthy monocytes displayed greater ubiquitination of IRS-2 and lower M2 polarization than allergic monocytes in response to IL-4 stimulation. Here, we identify SOCS1 as a key negative regulator of IL-4-induced IRS-2 signaling and M2 differentiation. Our findings provide novel insight into how dysregulated expression of SOCS increases IL-4 responses in allergic monocytes, and this may represent a new therapeutic avenue for managing allergic disease.Allergic asthma is an immune disorder characterized by elevation of total and specific IgE and infiltration of monocytes, lymphocytes, mast cells, eosinophils, and basophils in the lungs that causes inflammation and wheezing, cough, and dyspnea (1-4). A complex interplay of genetic and environmental factors contributes to the onset and maintenance of these diseases. Mechanistically, it is known that cytokines secreted from Th2 cells, such as interleukin (IL)-4, IL-5, IL-9, and IL-13, have a pivotal role in dictating the pathology of allergic disease (1, 2, 5, 6). The pathways by which IL-4 and IL-13 exert their biological effects have been a major focus of research and development of therapeutics to block their action through type I and II IL-4 receptors. Previously, we showed that in macrophages, IL-4 engagement of the type I IL-4 receptor resulted in robust tyrosine phosphorylation of insulin receptor substrate (IRS)-2, recruitment of p85 regulatory subunit of PI3K and GRB2, and strong induction of a subset of hallmark M2, also known as M(IL-4) (7), macrophage genes (8, 9). In contrast, IL-13 binding to the type II receptor resulted in only modest IRS-2 phosphorylation. Increasing the concentration of IL-13 did n...

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SOCS Proteins in Macrophage Polarization and Function

Cited by 140 publications

References 50 publications

The impact of surface chemistry modification on macrophage polarisation

The impact of surface chemistry modification on macrophage polarisation

Conditioned medium derived from rat amniotic epithelial cells confers protection against inflammation, cancer, and senescence

Suppressor of Cytokine Signaling (SOCS)1 Regulates Interleukin-4 (IL-4)-activated Insulin Receptor Substrate (IRS)-2 Tyrosine Phosphorylation in Monocytes and Macrophages via the Proteasome

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