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Mitochondria affect cellular functions alone or in cooperation with other cellular organelles. Recent research has demonstrated the close relationship of mitochondria with the endoplasmic reticulum (ER), both at the physical and the functional level. In an effort to define the combined effect of mitochondrial dysfunction (MD) and ER stress in the proinflammatory activities of macrophages, the human macrophage-like monocytic leukemia cell line THP-1 was treated with mitochondrial electron transport chain (ETC) blockers, and changes in the cellular responses upon stimulation by interferon (IFN)-[gamma] were analyzed. Inducing mitochondrial dysfunction (MD) with ETC blockers resulted in suppression of IFN-induced activation of JAK1 and STAT1/3, as well as the expression of STAT1-regulated genes. In addition, experiments utilizing pharmacological modulators of adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) and liver kinase B1 (LKBl)-deficient HeLa cells demonstrated that these suppressive effects are mediated by the LKB1-AMPK pathway. Treatment with pharmacological inhibitors of ER stress sensors failed to affect these processes, thus indicating that involvement of ER stress is not required. These results indicate that MD, induced by blocking the ETC, affects IFN-induced activation of JAK-STAT and associated inflammatory changes in THP-1 cells through the LKB1-AMPK pathway independently of ER stress. Key words: macrophage, inflammation, mitochondrial dysfunction, ER stress, JAK-STAT, AMPK. Les mitochondries affectent les fonctions cellulaires, seules ou en coopération avec d'autres organites cellulaires. La recherche récente a démontré une étroite relation entre la mitochondrie et le réticulum endoplasmique (RE), tant sur le plan physique que fonctionnel. Dans le but de définir les effets combinés de la dysfonction mitochondriale (DM) et du stress du RE sur les activités proinflammatoires des macrophages, la lignée cellulaire monocytique humaine de type macrophage THP-1 a été traitée avec des bloqueurs de la chaîne de transport d'électrons (CTE), et les changements des réponses cellulaires en réponse à une stimulation par l'interféron (IFN)-_ ont été analysés. L'induction de la dysfonction mitochondriale par les bloqueurs de la CTE donnait lieu à la suppression de l'activation de JAK1 et de STAT1/3 induite par l'IFN, de même que de l'expression des gènes régulés par STAT1. De plus, des expériences réalisées avec des modulateurs pharmacologiques de la protéine kinase activée par l'adénosine 5=-monophosphate (AMP) (AMPK) et des cellules HeLa déficientes en kinase B1 du foie (LKB1) ont démontré que ces effets suppresseurs sont médiés par la voie LKB1-AMPK. Un traitement avec des inhibiteurs pharmacologiques de détecteurs du stress du RE n'affectait pas ces processus, indiquant alors que l'implication du stress du RE n'est pas requise. Ces résultats indiquent que la dysfonction mitochondriale induite par le blocage de la CTE affecte l'activation de JAK-STAT induite par l'IFN et les changements inflammatoires associés chez les cellules THP1 par l'intermédiaire de la voie LKB1-AMPK de manière indépendante du stress du RE. [Traduit par la Rédaction] Mots-clés : macrophage, inflammation, dysfonction mitochondriale, stress du RE, JAK-STAT, AMPK., Introduction Mitochondria generate ATP by oxidative phosphorylation. This involves a redox reaction whereby electrons are transferred by the electron transport chain (ETC). Electrons are donated by nicotinamide adenine dinucleotide (NADH) [...]

Glucose-dependent insulinotropic polypeptide (GIP), a 42-aminoacid hormone, exerts multifaceted effects in physiology, most notably in metabolism, obesity, and inflammation. Its significance extends to neuroprotection, promoting neuronal proliferation, maintaining physiological homeostasis, and inhibiting cell death, all of which play a crucial role in the context of neurodegenerative diseases. Through intricate signaling pathways involving its cognate receptor (GIPR), a member of the G protein-coupled receptors, GIP maintains cellular homeostasis and regulates a defense system against ferroptosis, an essential process in aging. Our study, utilizing GIP-overexpressing mice and in vitro cell model, elucidates the pivotal role of GIP in preserving neuronal integrity and combating age-related damage, primarily through the Epac/Rap1 pathway. These findings shed light on the potential of GIP as a therapeutic target for the pathogenesis of ferroptosis in neurodegenerative diseases and aging. [BMB Reports 2024; 57(9): 417-423].

Background/aim: Skin wound healing is a physiological process restoring the structural and functional integrity of injured skin. During this process, wound management preventing bacterial infection and complications is important for the regeneration of skin layers and adnexa, as well as the protective function of the skin. Therefore, the development of an effective ointment to promote wound healing without complications is beneficial., Materials and Methods: This study developed Raepenol™ cream, comprising a base cream and natural compounds including paeonol, D-panthenol and extract of Centella asiatica, and assessed its therapeutic effect in wound healing. A rat model of skin wound healing and a mouse model of imiquimod-induced pruritus were employed. The effect of Raepenol™ cream was evaluated by wound size and histological analysis, including the integrity of skin structures and inflammatory response., Results: Raepenol™ cream treatment effectively restored the structural integrity of the skin in rats, including wound closure, regeneration of skin adnexa, and reconstitution of collagen, comparable to commercial ointment. Additionally, Raepenol™ cream significantly suppressed pruritus by inhibiting mast cell infiltration or retention in the inflammatory site of mouse ears., Conclusion: Raepenol™ cream effectively promoted wound healing and relieved pruritus in animal models. These results suggest that it could be a promising option for wound care and pruritus relief, offering potential advantages over current ointments., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: Inflammatory bowel disease (IBD) is characterized by dysregulated immune responses and a multifactorial etiology. While imatinib has demonstrated efficacy in the treatment of immune-related diseases, its potential effects in IBD treatment remain underexplored., Materials and Methods: This study aimed to investigate the therapeutic effects of imatinib in colitis treatment. A dextran sulfate sodium (DSS)-induced colitis model was used to mimic IBD in mice. Imatinib was administered orally to mice simultaneously with DSS treatment. The effects of imatinib on DSS-induced colitis were evaluated by analyzing colitis-related pathology, including the disease activity index (DAI), histological lesions, inflammatory markers, and tight junction integrity. Additionally, western blot analysis and quantitative real-time polymerase chain reaction were used to assess inflammatory markers, tight-junction proteins, and cell death., Results: In the DSS-induced colitis model, imatinib treatment exerted protective effects by attenuating weight loss, restoring colon length, reducing spleen weight, and improving the DAI score and histological lesions. Additionally, imatinib reduced the level of proinflammatory cytokines, including TNF-α, IL-6, and IL-1β. Furthermore, imatinib treatment restored tight-junction integrity and decreased the expression of apoptosis marker proteins., Conclusion: Overall, imatinib treatment significantly alleviated the symptoms of DSS-induced colitis by influencing the expression of proinflammatory cytokines, tight junction proteins, and apoptotic markers in mice. These findings highlight imatinib as a potential therapeutic candidate for IBD., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)