The effect of hypotensive drugs on mouse macrophage response to Staphylococcus aureus depends on the type of cell line

• Published in: Microbial pathogenesis Vol. 206; p. 107760
• Main Authors: Felkle, Dominik, Kaleta, Konrad, Sobocińska, Wiktoria, Zięba, Katarzyna, Czaja, Julia, Zyzdorf, Amanda, Jarczyński, Mateusz, Walczewska, Maria, Nowak, Bernadeta, Skalska, Paulina, Fedor, Angelika, Gębicka, Magdalena, Domagała, Angelika, Białecka, Anna, Bryniarski, Krzysztof, Nazimek, Katarzyna
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.09.2025
• Subjects: Amlodipine - pharmacology; Animals; Antihypertensive Agents - pharmacology; Antihypertensive drugs; Antimicrobial immunity; Captopril - pharmacology; Carvedilol - pharmacology; Cell Line; Cell Survival - drug effects; Cyclooxygenase 2 - metabolism; Cytokines - metabolism; Gram-positive bacteria; Hypertension; Hypotensive medication; Imidazoles - pharmacology; Macrophages; Macrophages - drug effects; Macrophages - immunology; Macrophages - microbiology; Mice; Nitric Oxide Synthase Type II - metabolism; Propranolol - pharmacology; RAW 264.7 Cells; Respiratory Burst - drug effects; Staphylococcus aureus - drug effects; Staphylococcus aureus - immunology; Tetrazoles - pharmacology; Verapamil - pharmacology; Hypertension; Antihypertensive drugs; Gram-positive bacteria; Antimicrobial immunity; Macrophages; Hypotensive medication
• ISSN: 0882-4010; 1096-1208; 1096-1208
• DOI: 10.1016/j.micpath.2025.107760

The growing prevalence of hypertension forces the widespread use of hypotensive drugs that are suspected to exert anti-inflammatory effects. However, their action on anti-infective immunity remains a subject of speculation. Therefore, our current study aimed to investigate the effects of selected hypotensive drugs, namely amlodipine, verapamil, captopril, olmesartan, carvedilol and propranolol, on the response of two mouse macrophage cell lines to Staphylococcus aureus by assessing their viability, secretory activity and expression of selected markers. Comparison of both cell lines, i.e., RAW 264.7 and J774A.1 macrophages, revealed the differences in their reactivity to Staphylococcus aureus and drug treatment, with RAW cell being more susceptible to the stimulation. Furthermore, bacteria more potently stimulated oxidative burst and cytokine release in RAW macrophages, and propranolol most efficiently modulated these processes. In addition, higher percentage of CD11b+ and CD86+ J774A.1 cells was detected, while expression level of these markers was upper on RAW macrophages. Both cell lines differed in cyclooxygenase-2 expression after bacterial stimulation. Moreover, the lack of arginase-1 expression with simultaneous iNOS expression suggested that RAW cells may be more prone to M1 polarization when exposed to bacteria. Interestingly, captopril, propranolol and verapamil were found to induce their effects more potently than olmesartan, carvedilol and amlodipine. However, in general all drugs exerted rather anti-inflammatory effects on naive macrophages and have not impaired macrophage response to Staphylococcus aureus. Thus, our findings provide a new perspective on the safety of antihypertensive therapy. •Mouse macrophage cell lines differently respond to bacteria and antihypertensives.•Hypotensive drugs do not impair antimicrobial activity of macrophages.•Verapamil has a stronger anti-inflammatory effect than amlodipine.•Captopril and olmesartan have similar immunomodulatory effects.•Propranolol-induced effects are more pronounced compared to carvedilol.