Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases ½

Palani, Chithra D.; Ramanathapuram, Lalitha; Lam‐ubol, Aroonwan; Kurago, Zoya B.

doi:10.18632/oncotarget.23784

Cited by 18 publications

(30 citation statements)

References 57 publications

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“…While other studies have demonstrated the functional role of IL-1 and signaling pathway of TLR4 in astrocytes 51,52 , to our knowledge, this is the first time the critical autocrine/paracrine effects of TNF-α on astrocyte functioning are demonstrated. In addition, other studies have demonstrated the roles of TLRs, including TLR2 and TLR4, in upregulating proliferation in various cancers [53][54][55][56] , to our knowledge, we are the first to demonstrate their significance in the transition between quiescent and proliferative astrocytes via the production of TNF-α. Our findings will likely delineate the cellular and molecular mechanisms involved in different neurological conditions.…”

Section: Discussionmentioning

confidence: 68%

Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha

Rodgers

Lin

Langan

et al. 2020

Sci Rep

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Acute inflammation is a key feature of innate immunity that initiates clearance and repair in infected or damaged tissues. Alternatively, chronic inflammation is implicated in numerous disease processes. The contribution of neuroinflammation to the pathogenesis of neurological conditions, including infection, traumatic brain injury, and neurodegenerative diseases, has become increasingly evident. Potential drivers of such neuroinflammation include toll-like receptors (TLRs). TLRs confer a wide array of functions on different cell types in the central nervous system (CNS). Importantly, how TLR activation affects astrocyte functioning is unclear. In the present study, we examined the role of TLR2/4 signaling on various astrocyte functions (i.e., proliferation, pro-inflammatory mediator production, regulatory mechanisms, etc) by stimulating astrocytes with potent exogenous TLR2/4 agonist, bacterial lipopolysaccharide (LPS). Newborn astrocytes were derived from WT, Tnfα −/− , Il1α −/− / Il1β −/− , and Tlr2 −/− /Tlr4 −/− mice as well as Sprague Dawley rats for all in vitro studies. LpS activated mRNA expression of different pro-inflammatory cytokines and chemokines in time-and concentrationdependent manners, and upregulated the proliferation of astrocytes based on increased 3 H-thymidine update. Following LPS-mediated TLR2/4 activation, TNF-α and IL-1β self-regulated and modulated the expression of pro-inflammatory cytokines and chemokines. Polyclonal antibodies against TNF-α suppressed TLR2/4-mediated upregulation of astrocyte proliferation, supporting an autocrine/paracrine role of tnf-α on astrocyte proliferation. Astrocytes perform classical innate immune functions, which contradict the current paradigm that microglia are the main immune effector cells of the CNS. TNF-α plays a pivotal role in the LpS-upregulated astrocyte activation and proliferation, supporting their critical roles in in cnS pathogenesis. Astrocytes are a specialized subtype of glia present throughout the central nervous system (CNS) 1. These star-shaped cells were initially described by German pathologist Rudolf Virchow as the "connective tissue of the brain". As a result of this dismissive analogy, astrocytes were long regarded as functionally insignificant 2. However, recent studies have revealed that astrocytes actually play diverse and critical roles in both CNS homeostasis and pathophysiology, many of which are currently being uncovered. Importantly, under normal circumstances, astrocytes are quiescent; however, in the presence of pathological stimuli, astrocytes re-enter the cell cycle, undergo morphological and biochemical changes, and produce pro-inflammatory cytokines 3,4. The molecular mechanisms underlying these changes remain unknown. One potential mechanism underlying this transition is the activation of toll-like receptors (TLRs). TLRs are a class of membrane-bound receptors called pattern recognition receptors (PRRs) that trigger innate immune responses. Innate immunity is a highly conserved system that is found in all animals an...

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Section: Discussionmentioning

confidence: 68%

Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha

Rodgers

Lin

Langan

et al. 2020

Sci Rep

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“…IHC was done as previously described . Briefly, 5 µm sections of formalin‐fixed paraffin‐embedded tissue were de‐paraffinized and rehydrated with ethanol.…”

Section: Methodsmentioning

confidence: 99%

“…IHC was done as previously described. 19 Briefly, 5 µm sections of formalin-fixed paraffin-embedded tissue were deparaffinized and rehydrated with ethanol. Antigen retrieval was done in water bath heating at 97°C with citrate buffer PH6 (Thermofisher).…”

Section: Immunohistochemistry (Ihc)mentioning

confidence: 99%

Role of dendritic cell‐mediated immune response in oral homeostasis: A new mechanism of osteonecrosis of the jaw

et al. 2020

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Dendritic cells are an important link between innate and adaptive immune response. The role of dendritic cells in bone homeostasis, however, is not understood.Osteoporosis medications that inhibit osteoclasts have been associated with osteonecrosis, a condition limited to the jawbone, thus called medication-related osteonecrosis of the jaw. We propose that disruption of the local immune response renders the oral microenvironment conducive to osteonecrosis. We tested whether zoledronate (Zol) treatment impaired dendritic cell (DC) functions and increased bacterial load in alveolar bone in vivo and whether DC inhibition alone predisposed the animals to osteonecrosis. We also analyzed the role of Zol in impairment of differentiation and function of migratory and tissue-resident DCs, promoting disruption of T-cell activation in vitro. Results demonstrated a Zol induced impairment in DC functions and an increased bacterial load in the oral cavity. DC-deficient mice were predisposed to osteonecrosis following dental extraction. Zol treatment of DCs in vitro caused an impairment in immune functions including differentiation, maturation, migration, antigen presentation, and T-cell activation. We conclude that the mechanism of Zolinduced osteonecrosis of the jaw involves disruption of DC immune functions required to clear bacterial infection and activate T cell effector response. K E Y W O R D S alveolar bone healing, dendritic cells, osteonecrosis 2596 | ELSAYED Et AL.

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“…[1][2][3][4][5] TLR2 promotes multiple cancers though the TLR2/MYD88 innate immune signal transduction adaptor (MyD88)/tumor necrosis factor (TNF) receptor associated factor 6 (TRAF66)/Jun proto-oncogene (Jun)/p38 MARK (p38)/mitogen-activated protein kinase (MAPK) (TLR2/MyD88/TRAF6/Jun/p38/MAPK) pathways. [6][7][8][9] The current study explored the ability of miR-144-5p to target TLR2 in glioblastoma cells after GS-Rd was administration. miR-144-5p was down-regulated in 4 types of glioblastoma cells ( Fig.…”

Section: Discussionmentioning

confidence: 99%

“…[1][2][3][4][5] The up-regulation of Toll-like receptor 2 (TLR2) is involved in the progression, migration, and poor clinical diagnosis of various cancers through multiple pathways. [6][7][8][9] In previous studies, TLR2 was validated as a target of miR-144-5p, and the expression of TLR2 can be inhibited by the overexpression of miR-144-5p. 10,11) Ginsenoside Rd (GS-Rd) has shown strong anti-tumor activity through inhibiting epidermal growth factor receptor (EGFR) signaling, oxidative stress, and protein kinase B (Akt)/mammarian target of rapamycin kinase (mTOR)/ ribosomal protein S6 kinase (p70S6K) (Akt/mTOR/p70S6K) signaling in various cancers.…”

Section: Introductionmentioning

confidence: 99%

Ginsenoside Rd Inhibits Glioblastoma Cell Proliferation by Up-Regulating the Expression of miR-144-5p

Liu

Sun

et al. 2020

Biological & Pharmaceutical Bulletin

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miR-144-5p exhibits anti-tumor activities in various cancers. Although treatment for glioblastoma has progressed rapidly, novel targets for glioblastoma are insufficient, particularly those used in precision medicine. In the current study, we found that ginsenoside Rd reduced the proliferation and migration of glioblastoma cells. Ginsenoside Rd up-regulated the tumor-suppressive miR-144-5p in glioblastoma cells. Moreover, Toll-like receptor 2, which is a target of miR-144-5p, was down-regulated. After inhibition of miR-144-5p, the effect of Ginsenoside Rd on proliferation inhibition and down-regulation of Toll-like receptor 2 was reduced. These data demonstrated the ginsenoside Rd/miR-144-5p/Toll-like receptor 2 regulatory nexus that controls the glioblastoma pathogenesis of glioblastoma. Our work provided novel targets for glioblastoma diagnosis and treatment.

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Toll-like receptor 2 induces adenosine receptor A2a and promotes human squamous carcinoma cell growth via extracellular signal regulated kinases ½

Cited by 18 publications

References 57 publications

Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha

Innate Immune Functions of Astrocytes are Dependent Upon Tumor Necrosis Factor-Alpha

Role of dendritic cell‐mediated immune response in oral homeostasis: A new mechanism of osteonecrosis of the jaw

Ginsenoside Rd Inhibits Glioblastoma Cell Proliferation by Up-Regulating the Expression of miR-144-5p

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