Klotho protects human monocytes from LPS-induced immune impairment associated with immunosenescent-like phenotype

Mytych, Jennifer; Romerowicz-Misielak, Maria; Koziorowski, Marek

doi:10.1016/j.mce.2017.05.003

Cited by 32 publications

(29 citation statements)

References 60 publications

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“…This is a follow-up project utilizing a model of klotho overexpression obtained in our previous study [3], however with a new batch of cells obtained from EACC (Sigma, Poznan, Poland). Human monocytic leukemia cells i.e.…”

Section: Cell Culture Klotho Overexpression and Lps/monensin Sodiummentioning

confidence: 99%

“…Protein lysates were prepared according to a prior study [3]. Briefly, cells were lysed in a RIPA buffer (radioimmunoprecipitation assay buffer) (50 mM Tris hydrochloride pH 7.5, 1% NP-40, 0.5% sodium deoxycholate, 0.1% SDS, 150 mM NaCl, 1 mM PMSF (phenylmethylsulfonyl fluoride), and 1 mM EDTA (ethylenediaminetetraacetic acid)).…”

Section: Protein Purification and Western Blotmentioning

confidence: 99%

“…Klotho was also reported to serve as an anti-inflammatory modulator since its depletion contributes to increased inflammation. In a previous paper, we showed how klotho plays a protective role in monocytes against the initiation of bacterial antigens-induced premature immunosenescence and the development of SASP, probably due to the inhibition of DNA damage [3]. Nevertheless, the role of klotho protein in other possible mechanisms of SASP development including Golgi and ER related stress pathways remains undiscovered.…”

Section: Introductionmentioning

confidence: 98%

“…Under conditions of chronic psychological stress, bacterial infections or exposure to certain persistent viral infections a so-called premature immunosenescence in younger individuals may occur [1,2]. In our previous papers, we have reported the possibility of initiation of premature immunosenescence in monocytes due to the treatment with bacterial antigens, which leads to several biochemical and functional changes [3,4]. Among these changes, the development of senescence-associated secretory phenotype (SASP) is observed.…”

Section: Introductionmentioning

confidence: 99%

“…Among these changes, the development of senescence-associated secretory phenotype (SASP) is observed. SASP is characterized by increased release of many factors into the cellular environment, including cytokines and pro-inflammatory chemokines, growth factors, or proteases and their modulators [3,4]. Considering the fact that prematurely senescent cells prolong their lifespan, do not undergo apoptosis, and retain their metabolic and secretory activity, SASP initiation is unfavorable and may lead to many abnormalities, including the development of chronic inflammation as a consequence of an imbalance between the amount of produced pro-inflammatory and anti-inflammatory factors.…”

Section: Introductionmentioning

confidence: 99%

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Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes

Mytych

Sołek

Będzińska

et al. 2020

Cells

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Immunosenescence in monocytes has been shown to be associated with several biochemical and functional changes, including development of senescence-associated secretory phenotype (SASP), which may be inhibited by klotho protein. To date, it was believed that SASP activation is associated with accumulating DNA damage. However, some literature data suggest that endoplasmic reticulum and Golgi stress pathways may be involved in SASP development. Thus, the aim of this study was to investigate the role of klotho protein in the regulation of immunosenescence-associated Golgi apparatus and ER stress response induced by bacterial antigens in monocytes. We provide evidence that initiation of immunosenescent-like phenotype in monocytes is accompanied by activation of CREB34L and TFE3 Golgi stress response and ATF6 and IRE1 endoplasmic reticulum stress response, while klotho overexpression prevents these changes. Further, these changes are followed by upregulated secretion of proinflammatory cytokines, which final modification takes place exclusively in the Golgi apparatus. In conclusion, we provide for the first time evidence of klotho involvement in the crosstalk on the line ER-Golgi, which may, in turn, affect activation of SASP. This data may be useful for a novel potential target for therapy in age-related and chronic inflammatory conditions.

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Section: Cell Culture Klotho Overexpression and Lps/monensin Sodiummentioning

confidence: 99%

Section: Protein Purification and Western Blotmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes

Mytych

Sołek

Będzińska

et al. 2020

Cells

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Clinical perspectives on the age-related increase of immunosuppressive activity

Salminen

2022

J Mol Med

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The aging process is associated with a remodeling of the immune system involving chronic low-grade inflammation and a gradual decline in the function of the immune system. These processes are also called inflammaging and immunosenescence. The age-related immune remodeling is associated with many clinical changes, e.g., risk for cancers and chronic infections increases, whereas the efficiency of vaccination and immunotherapy declines with aging. On the other hand, there is convincing evidence that chronic inflammatory states promote the premature aging process. The inflammation associated with aging or chronic inflammatory conditions stimulates a counteracting immunosuppression which protects tissues from excessive inflammatory injuries but promotes immunosenescence. Immunosuppression is a driving force in tumors and chronic infections and it also induces the tolerance to vaccination and immunotherapies. Immunosuppressive cells, e.g., myeloid-derived suppressor cells (MDSC), regulatory T cells (Treg), and type M2 macrophages, have a crucial role in tumorigenesis and chronic infections as well as in the tolerance to vaccination and immunotherapies. Interestingly, there is substantial evidence that inflammaging is also associated with an increased immunosuppressive activity, e.g., upregulation of immunosuppressive cells and anti-inflammatory cytokines. Given that both the aging and chronic inflammatory states involve the activation of immunosuppression and immunosenescence, this might explain why aging is a risk factor for tumorigenesis and chronic inflammatory states and conversely, chronic inflammatory insults promote the premature aging process in humans.

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Klotho modulates ER-mediated signaling crosstalk between prosurvival autophagy and apoptotic cell death during LPS challenge

2018

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Klotho protects human monocytes from LPS-induced immune impairment associated with immunosenescent-like phenotype

Cited by 32 publications

References 60 publications

Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes

Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes

Clinical perspectives on the age-related increase of immunosuppressive activity

Klotho modulates ER-mediated signaling crosstalk between prosurvival autophagy and apoptotic cell death during LPS challenge

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