Towards Age-Related Anti-Inflammatory Therapy: Klotho Suppresses Activation of ER and Golgi Stress Response in Senescent Monocytes
Jennifer Mytych,
Przemysław Sołek,
Agnieszka Będzińska,
Kinga Rusinek,
Aleksandra Warzybok,
Anna Tabęcka-Łonczyńska,
Marek Koziorowski
Affiliations
Jennifer Mytych
Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow Werynia 2, 36-100 Kolbuszowa, Poland
Przemysław Sołek
Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow Werynia 2, 36-100 Kolbuszowa, Poland
Agnieszka Będzińska
Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow Werynia 2, 36-100 Kolbuszowa, Poland
Kinga Rusinek
Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow Werynia 2, 36-100 Kolbuszowa, Poland
Aleksandra Warzybok
Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow Werynia 2, 36-100 Kolbuszowa, Poland
Anna Tabęcka-Łonczyńska
Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow Werynia 2, 36-100 Kolbuszowa, Poland
Marek Koziorowski
Department of Animal Physiology and Reproduction, Institute of Biology and Biotechnology, Collegium Scientarium Naturalium, University of Rzeszow Werynia 2, 36-100 Kolbuszowa, Poland
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.
