The Role of Mechanistic Target of Rapamycin (mTOR) Complexes Signaling in the Immune Responses

Soliman, Ghada A.

doi:10.3390/nu5062231

Cited by 69 publications

(53 citation statements)

References 194 publications

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“…For example, BCAAs have been shown to positively regulate mTOR, a Ser/Thr kinase that functions as a master regulator of various types of cellular processes, including protein synthesis, through Rag GTPase signaling. mTOR activity also promotes immune function, including reactive oxygen species (ROS) and cytokine production (42). It is thus possible that the fluctuations in BCAA concentrations result from complex host responses to bacterial infection.…”

Section: Discussionmentioning

confidence: 99%

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

et al. 2015

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Section: Discussionmentioning

confidence: 99%

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

et al. 2015

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“…In addition, the mTOR pathway has emerged as a regulator of the immune function. It is well known that mTOR is important in regulating adaptive immune activation and innate immune cell activation (Soliman, 2013;Weichhart & Säemann, 2008). On the other hand, mTOR seems to constrain full immune cell activation by upregulating the key anti-inflammatory cytokine IL-10 and inhibiting proinflammatory cytokines, including IL-6, TNF-a, and VEGF (Kirsch et al, 2012;Weichhart & Säemann, 2008;Zhang & Ma, 2014).…”

Section: Discussionmentioning

confidence: 99%

Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytesin vitrovia mTOR-signaling pathway

Liu

Yang

et al. 2015

Pharmaceutical Biology

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Context: The antidiabetic drug metformin exhibits antiproliferative and pro-apoptotic effects in various cells, suggesting its potential to treat a variety of malignant and non-malignant hyperplastic diseases. Clinical studies indicate that psoriasis patients with metformin treatment have a better response than those without metformin. Objective: The present study evaluates the antiproliferative activity and anti-inflammatory responses of metformin in human keratinocytes in vitro and explores the underlying mechanisms. Materials and methods: HaCaT cells were incubated with metformin at 0, 25, 50, and 100 mM for 48 h. Antiproliferative activity was evaluated by MTT and apoptotic response was examined by flow cytometry. ELISA was used to detect IL-6, TNF-a, and VEGF protein expression. Western blot was used to investigate the expression of the mammalian target of rapamycin (mTOR) and its downstream effectors p70 ribosomal S6 kinase (p70S6K). Results: The survival rates of HaCaT cells treated with metformin at 50 mM were reduced to 75.6, 59.4, and 30.3% at 24, 48, and 72 h, respectively. The number of apoptotic HaCaT cells was significantly increased at 50 mM metformin after 48 h treatment. Metformin can exert an antiinflammatory effect by direct inhibition of IL-6, TNF-a, and VEGF. Metformin at 50 mM significantly reduced the phosphorylation of mTOR and p70S6K, by 49.0 and 62.1%, respectively. Discussion and conclusion: Metformin treatment significantly inhibited proliferation and proinflammatory responses in HaCaT cells by a mechanism associated with inhibition of the mTOR signaling pathway. The results indicate that metformin may be used as a potential therapeutic agent for psoriasis.

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“…Leptin increases the expression of TNF-␣ in macrophages, a process that is mitigated by S6K1 inhibition (39). Given the role of mTOR/S6K1 regulation of innate and adaptive immunity in obesity, leptin modulation of mTOR/S6K1 signaling may be an important link between metabolism and immunity in regulating cardiovascular function in obesity (69).…”

Section: Leptin and Mtor/s6k Signalingmentioning

confidence: 99%

Overnutrition, mTOR signaling, and cardiovascular diseases

Jia

Aroor

Martinez‐Lemus

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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The prevalence of obesity and associated medical disorders has increased dramatically in the United States and throughout much of the world in the past decade. Obesity, induced by excess intake of carbohydrates and fats, is a major cause of Type 2 diabetes, hypertension, and the cardiorenal metabolic syndrome. There is emerging evidence that excessive nutrient intake promotes signaling through the mammalian target of rapamycin (mTOR), which, in turn, may lead to alterations of cellular metabolic signaling leading to insulin resistance and obesity-related diseases, such as diabetes, cardiovascular and kidney disease, as well as cancer. While the pivotal role of mTOR signaling in regulating metabolic stress, autophagy, and adaptive immune responses has received increasing attention, there remain many gaps in our knowledge regarding this important nutrient sensor. For example, the precise cellular signaling mechanisms linking excessive nutrient intake and enhanced mTOR signaling with increased cardiovascular and kidney disease, as well as cancer, are not well understood. In this review, we focus on the effects that the interaction between excess intake of nutrients and enhanced mTOR signaling have on the promotion of obesity-associated diseases and potential therapeutic strategies involving targeting mTOR signaling.

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The Role of Mechanistic Target of Rapamycin (mTOR) Complexes Signaling in the Immune Responses

Cited by 69 publications

References 194 publications

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

Importance of Branched-Chain Amino Acid Utilization in Francisella Intracellular Adaptation

Metformin inhibits proliferation and proinflammatory cytokines of human keratinocytesin vitrovia mTOR-signaling pathway

Overnutrition, mTOR signaling, and cardiovascular diseases

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