Tranilast Research Articles

Tranilast-matrine co-amorphous system: Strong intermolecular interactions, improved solubility, and physiochemical stability

There is a great interest to develop co-amorphous drug delivery systems to enhance the solubility of biopharmaceutics classification system (BCS) class II and IV drugs. However, most reported systems only resulted in severalfold solubility improvement. Tranilast (TRA) is an anti-allergic drug used to treat bronchial asthma and allergic rhinitis. It is a BCS class II drug and its poor aqueous solubility affects its absorption in vivo. To address this issue, a natural alkaloid matrine (MAR) with interesting biological activities was chosen to form a co-amorphous system with TRA, based on the solubility parameter and phase solubility experiment. The TRA-MAR drug-drug co-amorphous system was prepared by the solvent evaporation method, and further characterized by powder X-ray diffraction and modulated temperature differential scanning calorimetry. Fourier transform infrared spectroscopy, FT-Raman, and X-ray photoelectron spectroscopy revealed the formation of salt and the presence of strong intermolecular interactions in the TRA-MAR co-amorphous system, which are also supported by molecular dynamics simulations, showing ionic and hydrogen bonding interactions. This co-amorphous system exhibited excellent physical stability at both 25 °C and 40 °C under anhydrous silica gel condition. Finally, co-amorphous TRA-MAR showed greatly enhanced solubility (greater than 100-fold) and rapid release behavior in the vitro release experiments. NMR spectroscopy revealed the strong intermolecular interactions between TRA and MAR in both DMSO‑d6 and D2O. Our study resulted in a TRA-MAR co-amorphous drug system with significant solubility improvement and showcased the great potential to improve the dissolution behaviors of BCS class II and IV drugs through the co-amorphization approach.

Tranilast-tyrosine hybrid molecule exhibits dual activity: suppression of epithelial-mesenchymal transition and induction of cytotoxicity in cancer cells

The anti-allergic drug tranilast (TNL) reportedly exhibits inhibitory activity against epithelial-mesenchymal transition (EMT) at high concentrations. Herein, we synthesized a new hybrid molecule, tyrosine-conjugated TNL having a propyl linker (TNL-T), which is expected to increase anti-EMT activity by enhancing intracellular delivery through an amino acid transporter expressed in cancer cells. The anti-EMT activity of TNL-T was similar to that of TNL in the lung carcinoma cell line A549. Unlike TNL, TNL-T could induce dose-dependent cytotoxicity in A549 cells; this cytotoxicity was also observed in the glioblastoma cell lines U251 and U87. However, neither tyrosine nor TNL exhibited such cytotoxicity, demonstrating the importance of the TNL-T structure. The derivatization study showed that a derivative with an ethyl linker has the similar functions, and that of a pentyl linker was inactive. TNL-T, which exhibited dual activity by suppressing EMT and cancer cell proliferation, could aid in the development of new anticancer drugs.

Characterization of co-amorphous sinomenine-tranilast systems with strong intermolecular interactions and sustained release profiles

Drug co-amorphization is an emerging technology to improve the pharmacokinetic properties of drugs and overcome their side effects. Herein co-amorphization of sinomenine (SIN), an anti-rheumatoid arthritis alkaloid, and an antihistamine drug tranilast (TRA) was investigated for the sustained release of SIN and alleviating its histamine-release adverse reactions. The full co-amorphization of SIN-TRA was determined by powder X-ray diffraction and modulated temperature differential scanning calorimetry, while their CO2− and N+–H stretching vibrations in FTIR and protonated nitrogen signals in N 1s X-ray photoelectron spectra suggest the proton transfer between SIN and TRA. These intermolecular interactions could also be observed in their 1D and 2D NMR spectra. All co-amorphous samples exhibited sustained SIN release and excellent physical stability. Therefore, our study not only characterized the strong intermolecular interactions between SIN and TRA, but also discovered a promising drug combination strategy for the sustained release of SIN and reduction of its side effects.

Microchannel-embedded implantable device with fibrosis suppression for prolonged controlled drug delivery

For the prolonged, controlled delivery of systemic drugs, we propose an implantable drug-delivery chip (DDC) embedded with pairs of a microchannel and drug-reservoir serving as a drug diffusion barrier and depot, respectively. We pursued a DDC for dual drugs: a main-purpose drug, diclofenac (DF), for systemic exposure, and an antifibrotic drug, tranilast (TR), for local delivery. Thus, the problematic fibrotic tissue formation around the implanted device could be diminished, thereby less hindrance in systemic exposure of DF released from the DDC. First, we separately prepared DDCs for DF or TR delivery, and sought to find a proper microchannel length for a rapid onset and sustained pattern of drug release, as well as the required drug dose. Then, two distinct DDCs for DF and TR delivery, respectively, were assembled to produce a Dual_DDC for the concurrent delivery of DF and TR. When the Dual_DDC was implanted in living rats, the DF concentration in blood plasma did not drop significantly in the later periods after implantation relative to that in the early periods before fibrotic tissue formation. When the Dual_DDC was implanted without TR, there was a significant decrease in the blood plasma DF concentration as the time elapsed after implantation. Biopsied tissues around the Dual_DDC exhibited a significant decrease in the fibrotic capsule thickness and collagen density relative to the Dual_DDC without TR, owing to the effect of the local, sustained release of the TR.

Utility of a novel turn-off fluorescence probe for the determination of tranilast, an adjunctive drug for patients with severe COVID-19.

Tranilast (TR) could be investigated as a suitable anti-inflammatory and NLRP3 inflammasome inhibitor medication for the treatment of COVID-19 acute patients. Owing to its importance, our study was constructed for the determination of TR using a new, fast, sensitive, and reliable green spectrofluorimetric method. TR was quantified in this study by forming a complex with the acriflavine (AC) reagent. The reaction between TR and AC quenched the fluorescence of AC through the formation of an ion-association complex and the response was measured at 493 nm after excitation at 263 nm. It was observed that the quenching of the fluorescence of AC was linear (r = 0.9998) with the concentration of TR in the range of 1.0–15.0 μg mL−1. The limit of detection was 0.224 μg mL−1, and the limit of quantification was 0.679 μg mL−1. The fluorescence quenching mechanism was carefully studied and was confirmed to be able to analyze TR in its pure form and its prepared pharmaceutical dosage form. To validate the method, the international conference of harmonization (ICH) Q2R1 guidelines were followed. The statistical assessment of the proposed and comparison methods revealed no significant differences between them. Moreover, the green criteria of the method were evaluated and confirmed.

Tranilast treats cold-related hypertension by reducing the expression of NLRP3 inflammasome

Abstract Objective Cold exposure is associated with increased prevalence of hypertension and the related severe cardiovascular events. Aberrant activation of the nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome plays an important role in the development of hypertension. Tranilast (TR), an inhibitor of NLRP3, provides a useful pharmacological probe for exploring the role of NLRP3 in pathogenesis associated with inflammation and its potential application as a therapeutic agent. This study was designed to examine the effects of TR on NLRP3 and hypertension in rats exposed to cold environment to simulate the frigid-zone conditions. Methods and results Sprague Dawley (SD) rats were exposed to moderate cold temperature (4±1°C), and then were randomized to receive TR or vehicle for 3 weeks, while the control group was raised under rat room temperature (RT, 23±1°C). We found that cold exposure substantially increased blood pressure, NLRP3 inflammasome level, and fibrosis in aorta, which were reversed by TR. Conclusion TR has an anti-hypertensive property in cold environment, and this beneficial action is likely conferred by its inhibitory effects on inflammation and fibrosis. These findings suggest TR as a potential drug for the treatment of cold-induced hypertension.

Eletrophilic Chemistry of Tranilast Is Involved in Its Anti-Colitic Activity via Nrf2-HO-1 Pathway Activation.

Tranilast (TRL), a synthetic derivative of a tryptophan metabolite, is an anti-allergic drug used to treat bronchial asthma. We investigated how TRL activated the nuclear factor-erythroid 2 p45-related factor 2 (Nrf2)-hemeoxygenase-1 (HO-1) pathway based on the electrophilic chemistry of the drug and whether TRL activity contributed to the treatment of rat colitis. In human colon carcinoma cells, TRL activated Nrf2, as represented by an increase in nuclear Nrf2 and induction of Nrf2-dependent luciferase and, subsequently, HO-1, a target gene product of Nrf2. TRL activation of Nrf2 and induction of HO-1 were completely prevented by chemical reduction of the electrophilic functional group (α, β-unsaturated carbonyl group) in the drug. In parallel, TRL was reactive with the nucleophilic thiol group in N-acetylcysteine, forming a covalent adduct. Moreover, TRL, but not reduced TRL, binds to Kelch-like ECH-associated protein 1 (KEAP1), releasing Nrf2. TRL administration ameliorated colonic damage and inflammation in rats with dinitrobenzene sulfonic acid-induced colitis, which was partly compromised by the chemical reduction of TRL or co-treatment with an HO-1 inhibitor. Our results suggest that TRL activated the Nrf2-HO-1 pathway via covalent binding to KEAP1, partly contributing to TRL amelioration in rat colitis.

Tranilast-loaded amorphous solid dispersion prepared with fine droplet drying process for improvement of oral absorption and anti-inflammatory effects on chemically-induced colitis

The aim of the present study was to evaluate the applicability of a tranilast (TL)-loaded amorphous solid dispersion prepared with a fine droplet drying (FDD) process for the treatment of inflammatory bowel diseases. The FDD process, a novel powderization technology using an inkjet head, was employed to produce an amorphous solid dispersion of tranilast (ASD/TL). The physicochemical properties of ASD/TL were evaluated in terms of the morphology, particle size, crystallinity, drug-polymer interaction, and dissolution behavior. The oral absorption behavior of TL and anti-inflammatory effect on a chemically-induced colitis model were evaluated after oral administration of TL samples. The particle size of ASD/TL was 4 μm, and the span factor, one of the parameters to present the uniformity of particle size distribution, was calculated to be 0.28. In each ASD/TL particle, TL was dispersed in an amorphous state in the carrier polymer, and ASD/TL showed improved dissolution behavior of TL, as evidenced by a 2-times higher dissolution than the equilibrium solubility of crystalline TL even under acidic conditions. Orally-dosed ASD/TL exhibited rapid and improved oral absorption with 16-fold higher bioavailability than crystalline TL. ASD/TL could significantly attenuate the inflammatory symptoms in the colon tissues of colitis model rats based on the results of histological analyses and measurement of biomarkers. ASD/TL might contribute to the development of effective treatment for inflammatory bowel diseases due to its enhanced biopharmaceutical properties.

Tranilast abrogates cisplatin-induced testicular and epididymal injuries: An insight into its modulatory impact on apoptosis/proliferation.

Cisplatin is a chemotherapeutic agent whose therapeutic use is greatly limited by the associated organs' toxicity and particularly, testicular toxicity. Cisplatin-induced testicular damage reported being mediated through mitochondria-mediated apoptosis, inflammation, and oxidative stress. Evidence showed that tranilast (TRN) has the ability to restore the oxidative status and modulate TRAIL/caspase-8 signaling. This led us to hypothesize that TRN could abrogate cisplatin-induced testicular and epididymal injuries via inhibiting oxidative stress and modulating proliferation and TRAIL/caspase-8/cJNK signaling. Cisplatin injection induced oligospermia and abnormalities in testicular and epididymal structure along with impaired oxidative status. TRN administration (100 or 300 mg/kg) for 7 days post-cisplatin injection preserved spermatogenesis and restored testicular and epididymal architecture, but restoration was more so in TRN300 than TRN100. This was in line with the restoration of balanced oxidative status as indicated by the increased total antioxidant capacity, glutathione and superoxide dismutase activity, and the decreased malondialdehyde content in testes (p < 0.05 vs. cisplatin). TRN increased the cell proliferation revealed by the increased expression of proliferating cell nuclear antigen in a dose-dependent manner (p < 0.05 vs. cisplatin) whereas only TRN300 decreased testicular cJNK, TRAIL, and caspase-8 expression (p < 0.05 vs. cisplatin). Moreover, TRN dose-dependently inhibited the pro-inflammatory transcription factor NF-kB and the cytokine TNF-α expressions in testes. In conclusion, TRN300 was more effective than TRN100 in alleviating cisplatin-induced testicular and epididymal injuries and in enhancing spermatogenesis. This curative effect of TRN might be mediated through its antioxidant and anti-inflammatory impacts along with its modulatory impact on cJNK/TRAIL/caspase-8 signaling favoring proliferation rather than apoptosis.

Combination of hydroxyurea and tranilast suppresses gemcitabine resistance induced by ribonucleotide reductase M1 in gemcitabine‐resistant cells

AbstractIntroductionGemcitabine (GEM; 2′,2′‐difluorodeoxycytidine) is widely used to treat pancreatic, biliary tract, non‐small cell lung, bladder, mammary, and ovarian cancers. Chemoradiotherapy with GEM is a promising treatment for patients with advanced and locally recurrent head and neck cancers, including those with oral cavity cancer. However, the development of GEM resistance limits its use for curative treatment. Overexpression of ribonucleotide reductase (RR) M1 is a major cause of GEM resistance. We previously established RRM1‐mediated GEM‐resistant cell lines (MGEM6 and MGEM8) and showed that the knockdown of RRM1 is a rationale strategy for overcoming GEM resistance. We further investigated the role of RR inhibition in enhancing the effects of GEM.Materials and methodsWe examined whether the combination treatment of hydroxyurea (HU), 3‐aminopyridine‐2‐carboxaldehyde thiosemicarbazone (3‐AP), and tranilast (TRL) could increase GEM sensitivity using the survival assay of MGEM6, MGEM8, and their parental cells. The effects of these compounds on the expression of RRM1 and RRM2 mRNA and protein were evaluated in the three cell lines by quantitative PCR (polymerase chain reaction) and immunoblotting.ResultsHU or/and TRL at nontoxic concentrations significantly improved the response of resistant cancer cells to GEM, whereas 3‐AP did not. This may have been because the two agents reduced the ratio of RRM1/RRM2. The three compounds have different effects on the mRNA and protein expression of RRM1 and RRM2.ConclusionsThe combination of HU and/or TRL with GEM enhances the toxic effect in gemcitabine‐resistant cells induced by RRM1.

Tranilast Directly Targets NLRP3 to Protect Melanocytes From Keratinocyte-Derived IL-1β Under Oxidative Stress.

The activation of NLRP3 inflammasome-IL-1β pathway in keratinocytes contributes to the melanocyte death via autoimmunity-dependent manner in vitiligo. As a safe small-compound drug employed frequently in clinic, tranilast (TR) is newly reported to block the activation of NLRP3 inflammasome in macrophage. Nevertheless, whether keratinocyte-derived IL-1β damages melanocytes in an autoimmunity-independent way and whether TR could ameliorate the melanocyte damage via inhibiting the NLRP3-IL-1β pathway in keratinocyte still are not clear. In the present study, we initially found that TR could impede the secretion of IL-1β from keratinocytes by interfering the NLRP3 oligomerization. More importantly, we illustrated that TR could decrease the melanocyte apoptosis, improve the melanogenesis, and have the capacity to optimize the melanosome translocation by abolishing the keratinocyte-derived IL-1β. Additionally, TR could mitigate the secretion of inflammatory cytokines such as IL-6, IL-8, TNF-α, and IL-18 in keratinocytes under oxidative stress. In short, our data indicate that IL-1β plays detrimental roles in the melanocyte survival, melanogenesis, melanosome translocation and the secretion of inflammatory cytokines, and TR could be a promising therapeutic strategy in vitiligo by attenuating the keratinocyte-derived IL-1β under oxidative stress.

Enhanced nose-to-brain delivery of tranilast using liquid crystal formulations

Intranasal administration is poised as a competent method in delivering drugs to the brain, because the nasal route has a direct link with the central nervous system bypassing the formidable blood-brain barrier. C17-monoglycerol ester (MGE) and glyceryl monooleate (GMO) as liquid crystal (LC)-forming lipids possess desirable formulation characteristics as drug carriers for intranasally administered drugs. This study investigated the effect of LC formulations on the pharmacokinetics of tranilast (TL), a lipophilic model drug, and its distribution in the therapeutic target regions of the brain in rats. The anatomical biodistribution of LC formulations was monitored using micro-computed tomography tandem in vivo imaging systems. MGE and GMO effectively formed LC with suitable particle size, zeta potential, and viscosity supporting the delivery of TL to the brain. MGE and GMO LC formulations enhanced brain uptake by 10- to 12-fold and 2- to 2.4- fold, respectively, compared with TL solution. The olfactory bulb had the highest TL concentration and fluorescent signals among all the brain regions, indicating a direct nose-to-brain delivery pathway of LC formulations. LC-forming lipids, MGE and GMO, are potential biomaterials in formulations intended for intranasal administration.

173 Tranilast directly targets NLRP3 to protect melanocytes from keratinocyte-derived IL-1β under oxidative stress

Vitiligo is a kind of oxidative-mediated inflammatory disease characterized by the death of melanocytes. Recent studies have indicated that the activation of NLRP3 inflammasome-IL-1β pathway in keratinocyte contributed to melanocytes death via disturbing the local immunity in the pathogenesis of vitiligo. Notably, as a safe small-compound drug employed frequently in clinic, tranilast (TR) is reported to block the activation of NLRP3 inflammasome in macrophage. Nevertheless, whether TR could improve the melanocyte damage exerted by microenvironment, especially constituted by keratinocytes, via inhibiting the NLRP3-IL-1β pathway of keratinocytes is not clear.

Development of Sustained-Release Ophthalmic Formulation Based on Tranilast Solid Nanoparticles.

Eye drops containing Tranilast (TL), N-(3,4-dimethoxycinnamoyl) anthramilic acid, are used as an anti-allergic conjunctivitis drug in the ophthalmic field. Traditional eye drops are very patient compliant, although the bioavailability (BA) of most eye drops is low since eye drops cannot be instilled beyond the capacity of the conjunctival sac due to its limited volume. Thus, traditional eye drops have low BA and a short duration of the drug on the ocular surface, so solutions to these problems are highly anticipated. In this study, we designed a sustained-release drug-delivery system (DDS) for TL nanoparticles. TL nanoparticles were prepared by bead mill treatment, and the gel formulations containing TL nanoparticles (TL-NPs-Gel, particle size 50 nm–100 nm) were provided by carboxypolymethylene. The crystal structure of TL with and without bead mill treatment is the same, but the TL solubility in formulations containing nanoparticles was 5.3-fold higher compared with gel formulations containing TL microparticles (TL-MPs-Gel). The photo and thermal stabilities of TL-NPs-Gel are also higher than those of dissolved TL. Moreover, when TL-NPs-Gel is applied to the upper eyelid skin (outside), the TL is released as nanoparticles, and delivered to the lacrimal fluid through the meibomian glands. In addition, the TL release profile for TL-NPs-Gel was sustained over 180 min after the treatment. These findings can be used to develop a sustained-release DDS in the ophthalmic field.

Tranilast attenuates methotrexate-induced renal and hepatic toxicities: Role of apoptosis-induced tissue proliferation.

Drug-induced organ toxicity is a frequently encountered obstacle in the field of medical practice that limits the use of numerous pharmacologically valuable drugs. Methotrexate (MTX)-induced organ toxicity is unfortunately the rate-limiting factor for its clinical application. In the current study, MTX injection induced significant renal and hepatic toxicities manifested on functional, biochemical, and histopathological scales. This was associated with a significant elevation in both renal and hepatic contents of TNF-related apoptosis-inducing ligand (TRAIL) and caspase-8, biomarkers of tissue apoptosis. Inline, immunohistochemical analysis confirmed that tissue increased expression of Ki67 as a biomarker of tissue regeneration in both organs. Tranilast (TRAN) is a small molecular weight anti-inflammatory and antiallergic agent. TRAN's coadministration with MTX in the current study induced a significant tissue recovery via modulation of TRAIL/caspase-8 signaling and modulation of apoptosis-induced tissue proliferation confirmed by quantification of Ki67 expression. In conclusion, TRAN can be proposed as an effective drug to attenuate MTX-induced organ toxicity via modulation of apoptosis-induced tissue proliferation pathway.

Screening and evaluation of potential inhibitors against vaccinia virus from 767 approved drugs.

The development of therapies for human smallpox is needed due to the increasing concern over the potential use of smallpox virus as a biological weapon. Here, we report a high-throughput screening for anti-smallpox virus drugs from a 767-small-molecule library, employing two vaccinia virus (VACV) strains containing firefly luciferase (VTT-Fluc and VG9-Fluc) as surrogate viruses. Using an eight-point dose response format assay, 26 compounds of different pharmacological classes were identified with in vitro anti-VACV activities. Mycophenolate mofetil (MMF) and tranilast (TRA) were detected to possess the highest anti-VACV potency (selectivity index values of >334 and >74, respectively); they could inhibit VTT-Fluc replication in nude mice at 5 days post-infection by 99% (10 mg/kg, P < .01) and 59% (45 mg/kg, P = .01), respectively, as indicated by bioluminescent intensity. In conclusion, MMF and TRA are promising anti-smallpox virus candidates for further optimization and repurposing for use in clinical practice.

Evaluation of cationic channel TRPV2 as a novel biomarker and therapeutic target in Leukemia-Implications concerning the resolution of pulmonary inflammation

Patients treated during leukemia face the risk of complications including pulmonary dysfunction that may result from infiltration of leukemic blast cells (LBCs) into lung parenchyma and interstitium. In LBCs, we demonstrated that transient receptor potential vanilloid type 2 channel (TRPV2), reputed for its role in inflammatory processes, exhibited oncogenic activity associated with alteration of its molecular expression profile. TRPV2 was overexpressed in LBCs compared to normal human peripheral blood mononuclear cells (PBMCs). Additionally, functional full length isoform and nonfunctional short form pore-less variant of TRPV2 protein were up-regulated and down-regulated respectively in LBCs. However, the opposite was found in PBMCs. TRPV2 silencing or pharmacological targeting by Tranilast (TL) or SKF96365 (SKF) triggered caspace-mediated apoptosis and cell cycle arrest. TL and SKF inhibited chemotactic peptide fMLP-induced response linked to TRPV2 Ca2+ activity, and down-regulated expression of surface marker CD38 involved in leukemia and lung airway inflammation. Challenging lung airway epithelial cells (AECs) with LBCs decreased (by more than 50%) transepithelial resistance (TER) denoting barrier function alteration. Importantly, TL prevented such loss in TER. Therefore, TRPV2 merits further exploration as a pharmacodynamic biomarker for leukemia patients (with pulmonary inflammation) who might be suitable for a novel [adjuvant] therapeutic strategy based on TL.

Cannabidiol Increases Proliferation, Migration, Tubulogenesis, and Integrity of Human Brain Endothelial Cells through TRPV2 Activation.

The effect of cannabidiol (CBD), a high-affinity agonist of the transient receptor potential vanilloid-2 (TRPV2) channel, has been poorly investigated in human brain microvessel endothelial cells (BMEC) forming the blood-brain barrier (BBB). TRPV2 expression and its role on Ca2+ cellular dynamics, trans-endothelial electrical resistance (TEER), cell viability and growth, migration, and tubulogenesis were evaluated in human primary cultures of BMEC (hPBMEC) or in the human cerebral microvessel endothelial hCMEC/D3 cell line. Abundant TRPV2 expression was measured in hCMEC/D3 and hPBMEC by qRT-PCR, Western blotting, nontargeted proteomics, and cellular immunofluorescence studies. Intracellular Ca2+ levels were increased by heat and CBD and blocked by the nonspecific TRP antagonist ruthenium red (RR) and the selective TRPV2 inhibitor tranilast (TNL) or by silencing cells with TRPV2 siRNA. CBD dose-dependently induced the hCMEC/D3 cell number (EC50 0.3 ± 0.1 μM), and this effect was fully abolished by TNL or TRPV2 siRNA. A wound healing assay showed that CBD induced cell migration, which was also inhibited by TNL or TRPV2 siRNA. Tubulogenesis of hCMEC/D3 cells in 3D matrigel cultures was significantly increased by 41 and 73% after a 7 or 24 h CBD treatment, respectively, and abolished by TNL. CBD also increased the TEER of hPBMEC monolayers cultured in transwell, and this was blocked by TNL. Our results show that CBD, at extracellular concentrations close to those observed in plasma of patients treated by CBD, induces proliferation, migration, tubulogenesis, and TEER increase in human brain endothelial cells, suggesting CBD might be a potent target for modulating the human BBB.

A case of cutaneous sarcoidosis treated with tranilast

A case of cutaneous sarcoidosis treated with tranilast

Ca2+ Signaling and IL-8 Secretion in Human Testicular Peritubular Cells Involve the Cation Channel TRPV2.

Peritubular cells are part of the wall of seminiferous tubules in the human testis and their contractile abilities are important for sperm transport. In addition, they have immunological roles. A proteomic analysis of isolated human testicular peritubular cells (HTPCs) revealed expression of the transient receptor potential channel subfamily V member 2 (TRPV2). This cation channel is linked to mechano-sensation and to immunological processes and inflammation in other organs. We verified expression of TRPV2 in peritubular cells in human sections by immunohistochemistry. It was also found in other testicular cells, including Sertoli cells and interstitial cells. In cultured HTPCs, application of cannabidiol (CBD), a known TRPV2 agonist, acutely induced a transient increase in intracellular Ca2+ levels. These Ca2+ transients could be blocked both by ruthenium red, an unspecific Ca2+ channel blocker, and tranilast (TRA), an antagonist of TRPV2, and were also abolished when extracellular Ca2+ was removed. Taken together this indicates functional TRPV2 channels in peritubular cells. When applied for 24 to 48 h, CBD induced expression of proinflammatory factors. In particular, mRNA and secreted protein levels of the proinflammatory chemokine interleukin-8 (IL-8/CXCL8) were elevated. Via its known roles as a major mediator of the inflammatory response and as an angiogenic factor, this chemokine may play a role in testicular physiology and pathology.