Residue-Specific Message Encoding in CD40-Ligand

Sarode, Aditya; Jha, Mukesh Kumar; Zutshi, Shubhranshu; Ghosh, Sayani; Mahor, Hima; Sarma, Uddipan; Saha, Bhaskar

doi:10.1016/j.isci.2020.101441

Cited by 15 publications

(13 citation statements)

References 62 publications

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“…Tbet, Gata3, Rorγt, and Foxp3 expression levels as well as the expression of CD4 + T cell surface markers such as CD69, CD39, CD132, CD122, CD28, CXCR5, CCR1, CCR6 were not significantly different. CD40L is a co-stimulatory receptor on Tfh cells [ 26 ] and also helps in immunoglobulin class switching, but there is no significant difference between GCB, Tfh cells, and concentrations of IgM and other immunoglobulins, indicating that expression of CD40L is similar in young WT and AMPK-KO mice. We have previously showed similar expression of Treg surface markers, except PD-1, Nrp1, and ICOS [ 14 ], suggesting that the newly generated young WT and AMPK-KO mice are almost phenotypically similar and have similar Th1, Th2, Th17, and Treg transcriptional profiles.…”

Section: Discussionmentioning

confidence: 99%

AMPK Amplifies IL2–STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice

Pokhrel

Kang

Timilshina

et al. 2022

IJMS

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AMP-activated protein kinase (AMPK), an important regulator of the aging process, is expressed in various immune cells. However, its role in regulatory T cell (Treg) stability during aging is poorly understood. Here, we addressed the role of AMPK in Treg function and stability during aging by generating Treg-specific AMPKα1 knockout mice. In this study, we found that AMPKα1-deficient Tregs failed to control inflammation as effectively as normal Tregs did during aging. AMPK knockout from Tregs reduces STAT5 phosphorylation in response to interleukin (IL)-2 stimulation, thereby destabilizing Tregs by decreasing CD25 expression. Thus, our study addressed the role of AMPK in Tregs in sensing IL-2 signaling to amplify STAT5 phosphorylation, which, in turn, supports Treg stability by maintaining CD25 expression and controlling inflamm-aging.

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Section: Discussionmentioning

confidence: 99%

AMPK Amplifies IL2–STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice

Pokhrel

Kang

Timilshina

et al. 2022

IJMS

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“…It is unclear how alcohol activates p38γ MAPK. It has been proposed that the interaction of several upstream signaling molecules, such as CD40L and CD40, may result in p38 MAPK activation which stimulates diverse cytokine profile, transcription factors and oxidative stress ( 46 ). These processes may be involved metastasis or cancer stemness.…”

Section: Discussionmentioning

confidence: 99%

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice

Li,

Xu,

Chen

et al. 2024

Front. Oncol.

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PurposeAlcohol consumption increases the risk of breast cancer and promotes cancer progression. Alcohol exposure could affect both processes of the mammary carcinogenesis, namely, the cell transformation and onset of tumorigenesis as well as cancer aggressiveness including metastasis and drug resistance/recurrence. However, the cellular and molecular mechanisms underlying alcohol tumor promotion remain unclear. There are four members of the mammalian p38 mitogen-activated protein kinase (MAPK) family, namely, p38α, p38β, p38γ and p38δ. We have previously demonstrated alcohol exposure selectively activated p38γ MAPK in breast cancer cells in vitro and in vivo. Pirfenidone (PFD), an antifibrotic compound approved for the treatment of idiopathic pulmonary fibrosis, is also a pharmacological inhibitor of p38γ MAPK. This study aimed to determine whether PFD is useful to inhibit alcohol-induced promotion of breast cancer.MethodsFemale adolescent (5 weeks) MMTV-Wnt1 mice were exposed to alcohol with a liquid diet containing 6.7% ethanol. Some mice received intraperitoneal (IP) injection of PFD (100 mg/kg) every other day. After that, the effects of alcohol and PFD on mammary tumorigenesis and metastasis were examined.ResultsAlcohol promoted the progression of mammary tumors in adolescent MMTV-Wnt1 mice. Treatment of PFD blocked tumor growth and alcohol-promoted metastasis. It also significantly inhibited alcohol-induced tumorsphere formation and cancer stem cell (CSC) population.ConclusionPFD inhibited mammary tumor growth and alcohol-promoted metastasis. Since PFD is an FDA-approved drug, the current findings may be helpful to re-purpose its application in treating aggressive breast cancer and alcohol-promoted mammary tumor progression.

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“…Activation of ERK1/2 by PMA was subsequently demonstrated to be a prerequisite in committing K562 and other such cell lines to undergo megakaryocytic differentiation (Conde et al, 2010, Whalen et al, 1997). In addition, ERK activation by sCD40L was also shown to activate ERK leading to inhibition of cell proliferation and induction of apoptosis in K562 cells (Ren et al, 2016; Sarode et al, 2020). In agreement with these, we also observed that ORM indeed activated ERK1/2 and growth suppressor proteins p21 and p27 leading to growth arrest so that cells can exit the cell cycle and undergo differentiation.…”

Section: Discussionmentioning

confidence: 99%

Ormeloxifene, a nonsteroidal antifertility drug promotes megakaryocyte differentiation in leukemia cell line K562

Mishra

Singh

Thacker

et al. 2023

Cell Biology International

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Ormeloxifene (ORM) (3,4‐trans‐2,2‐dimethyl‐3‐phenyl‐4‐p‐(β‐pyrrolidinoethoxy) phenyl‐7‐methoxychroman), world's first nonsteroidal selective estrogen receptor modulator approved for contraception in India has been shown to have potential anticancer activities. Here, we show that ORM can induce megakaryocyte and myeloid (granulocytic) but not erythroid differentiation in multipotent human myeloid leukemia cell line K562. We show that ORM at an IC50 of 7.5 µM can induce morphological changes similar to megakaryocytes in K562 cells. ORM led to increase in levels of megakaryocytic differentiation markers (CD41 and CD61) as well as key transcription factors GATA1 and AML1. We further show that ORM induces megakaryocytic differentiation in K562 cells through ERK activation and induction of autophagy in a fashion similar to other known inducers of megakaryocytic differentiation such as phorbol esters. In addition, as shown earlier, we yet again observed that ORM led to activation of caspases since their inhibition through pan‐caspase inhibitor mitigated megakaryocytic differentiation as they led to significant decrease in CD41 and CD61. Because induction of megakaryocytic differentiation in K562 involves growth arrest and exit from cell cycle, we also observed an increase in levels of p21 and p27 with decrease in c‐Myc protein levels in K562 cells treated with 7.5 µM ORM for 24 and 48 h, respectively. Taken together, these findings indicate that ORM can markedly induce megakaryocytic differentiation in K562 cells.

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Residue-Specific Message Encoding in CD40-Ligand

Cited by 15 publications

References 62 publications

AMPK Amplifies IL2–STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice

AMPK Amplifies IL2–STAT5 Signaling to Maintain Stability of Regulatory T Cells in Aged Mice

Pirfenidone ameliorates alcohol-induced promotion of breast cancer in mice

Ormeloxifene, a nonsteroidal antifertility drug promotes megakaryocyte differentiation in leukemia cell line K562

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