Cigarette smoke (CS) is a well-known source of several inflammatory, cytotoxic and genotoxic compounds that cause chronic lung diseases. The transient receptor potential ankyrin 1 (TRPA1), a smoking-responsive, non-selective cation channel, is expressed by both capsaicin-sensitive peptidergic sensory nerves and non-neuronal cells of the lung, but there are few and controversial data on its expression and function on macrophages. Here, we investigated TRPA1 mRNA and protein expression in mouse and human lung tissues and human 3D spheroids, with a particular focus on its expression and potential regulatory effects on pro- and anti-inflammatory macrophage functions in response to CS. TRPA1 was stably expressed in both human and mouse alveolar macrophages, being upregulated after CS exposure and its functional activity was demonstrated in mouse macrophage culture. Moreover, besides CS, the TRPA1 genotype itself affected the expression of M1- (Il-1β, Il-23) and M2-type (Il-10, Tgfβ) macrophage cytokines. Furthermore, CS extract increased TRPA1 mRNA in human lung spheroids showing more prominent expression in macrophage-containing 3D aggregates, while CS extract influenced an elevated TGFβ expression specifically in macrophage-containing spheroids. These results suggest the fine-tuning role of TRPA1 activation in CS-induced airway inflammation, particularly in macrophages, but further studies are needed to draw precise conclusions.

Endometriosis is the extrauterine engraftment of endometrium-like tissue, causing chronic pain. Complex sensory–vascular–immune interactions, including growth factors, cytokines, and neuropeptides, are implicated in its pathophysiology, but the mechanisms remain unknown. Here, epidermal growth factor (EGF), vascular endothelial growth factor, interleukins (IL-1β, IL-6, IL-8), macrophage migration inhibitory factor (MIF), calcitonin gene-related peptide, and somatostatin were measured in the serum of endometriosis patients with different disease severities, menstruation cycle- and pharmacotherapy-related hormonal status compared with controls. Mediator levels in deep-infiltrating rectosigmoid nodules were also compared with those in non-endometriotic colon tissues. Pain was assessed by the visual analogue scale. Serum EGF was significantly lower in mild endometriosis and in the secretory phase. MIF and IL-6 were higher in stage I–IV endometriosis, with MIF also higher in the secretory phase and in patients not receiving oral contraceptives. Somatostatin was lower in mild endometriosis than that in healthy individuals and the severe endometriosis group. No tissue-level differences were found. A strong positive correlation between serum EGF and somatostatin levels and dysmenorrhea and dysuria was detected in mild cases. It is concluded that certain serum alterations may be related to severity- and hormone status-dependent endometriosis mechanisms, but their diagnostic/prognostic value seems to be limited due to variability and lack of specificity.

Transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) have been implicated in cancer biology, but their functional relevance in prostate adenocarcinoma (PAC) remains unclear. Therefore, we characterized TRPA1/TRPV1 expression and function in benign prostatic hyperplasia (BPH), PAC tissues, and PAC cell lines with different characteristics and examined the effects of their agonists on cancer-cell viability. TRPA1 and TRPV1 transcripts were assessed by RNAscope in situ hybridization and RT-qPCR, channel activity by Fura-2-based Ca²⁺ imaging, and viability/proliferation by ATP-based luminescence and automated cell counting. TRPA1 and/or TRPV1 mRNAs were detected in PAC tissues and cell lines, but selective stimulation with allyl-isothiocyanate (AITC) or capsaicin did not evoke Ca²⁺ influx, indicating no detectable functional channel activity under our experimental conditions. Non-selective TRPA1 activators induced Ca²⁺ influx responses that were not inhibited by the receptor antagonist A-967079. AITC concentration dependently reduced viability and proliferation of the androgen-sensitive 22Rv1 and LNCaP cells, and these effects were not prevented by TRPA1 antagonists. Capsaicin had no effect at TRPV1-selective concentrations. Thus, transcript expression does not predict functional TRPA1/TRPV1 activity in PAC cells, and AITC reduces PAC-cell viability through TRPA1-independent mechanisms.