Comparison of serum and synovial fluid IL-1β, IL-18, TNF-α and Caspase-1 levels between OA knee patients taking Colchicine vs NSAIDS

Knee osteoarthritis (KOA) is a common chronic disease in the elderly and leads to a high rate of disability. Du Huo Ji Sheng Tang (DHJST), a Chinese traditional medicinal formula, is a classic prescription for the treatment of KOA. Here, we investigated whether DHJST could inhibit inflammation and treat KOA through suppressing NLRP3/nuclear factor (NF)-κB inflammatory signals in rats. The serum levels of interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor (TNF)-α, NLRP3, ASC, Caspase-1, p-NF-κB-P65, and p-IκBa were detected in healthy adults and patients with KOA before and after treatment. Sprague Dawley (SD) rats were divided into normal group, model group, diclofenac sodium group (5 mg/kg), DHJST high-dose group (1 g/kg), and DHJST low-dose group (0.5 g/kg). The right hind knee joint of the rats, except normal group, was injected with 4% papain (0.25 mL/kg) once every 7 days for three times. All rats were treated for 3 weeks. The swelling volume of right hind paw; five classification of inflammatory cells in synovial fluid; pathological changes of the knee-joint synovial membrane and cartilage; levels of IL-1β, IL-6, and TNF-α in serum and knee-joint synovial fluid; and the expressions of NLRP3/NF-κB inflammatory signals in the knee-joint synovial membrane were detected. The serum levels of IL-1β, IL-6, IL-10, TNF-α, NLRP3, ASC, Caspase-1, p-NF-κB-P65, and p-IκBa in KOA patients treated with DHJST were significantly decreased. The KOA rats treated with DHJST showed significant decreases in swelling volume of right hind paws; the percentage of leukocyte, lymphocyte, neutrophil, and eosinophils in synovial fluid; the levels of IL-1β, IL-6, and TNF-α in serum and knee-joint synovial fluid; and the expressions of NLRP3 ASC, Caspase-1, IL-1β, p-NF-κB-P65, and p-IκBa in the knee-joint synovial membrane, and showed an alleviation in pathological changes of the knee-joint synovial membrane and cartilage. Our data provide the first evidence that DHJST relieves KOA via suppressing NLRP3/NF-κB inflammatory signals in rats

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Caspase-1 Level in Synovial Fluid Is High in Patients with Spondyloarthropathy but Not in Patients with Gout

Journal of Korean Medical Science ◽

10.3346/jkms.2013.28.9.1289 ◽

2013 ◽

Vol 28 (9) ◽

pp. 1289 ◽

Cited By ~ 7

Author(s):

Chang-Nam Son ◽

So-Young Bang ◽

Ji Hae Kim ◽

Chan-Bum Choi ◽

Tae-Hwan Kim ◽

...

Keyword(s):

Synovial Fluid ◽

Caspase 1

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Trifluorobenzamidine prevents allergic rhinitis by regulating IgE, IL-4 and IL-5 in T-cells

Tropical Journal of Pharmaceutical Research ◽

10.4314/tjpr.v19i5.17 ◽

2020 ◽

Vol 19 (5) ◽

pp. 1023-1029

Author(s):

Yongbo Zhang ◽

Zhuo Wu ◽

Yihui Yang ◽

Lu Ding

Keyword(s):

Allergic Rhinitis ◽

Serum Levels ◽

Eosinophil Infiltration ◽

Spleen Weight ◽

Caspase 1 ◽

Tnf Α ◽

Cytokine Levels ◽

Enzymelinked Immunosorbent Assay ◽

Inhibitory Potential ◽

New Treatment

Purpose: To investigate the effect of trifluorobenzamidine (TBI) on a mouse model of ovalbumin (OVA)- induced allergic rhinitis. Methods: Allergic rhinitis was established in mice via sensitization on days 1, 5 and 14 through intraperitoneal injection of OVA (100 μg) in PBS. On day 15, the mice were subjected to intranasal exposure to OVA (1.5 mg dissolved in PBS). Prior to 10 days of intranasal exposure to OVA, the micewere treated with TBI at doses of 5, 10 and 20 μg/kg. Cytokine levels were determined using enzymelinked immunosorbent assay (ELISA) kits, while cyclooxygenase (COX)-2 and caspase-1 activity were assayed with western blotting. Results: Treatment with TBI significantly (p < 0.05) reduced OVA-mediated increases in nasal rub scores, and decreased serum levels of IgE, TNF-α, thymic stromal lymphopoietin (TSLP), IL-1β and histamine in mice. It also significantly regulated spleen weight and IL-4 secretion (p < 0.05) in OVAadministered mice. TBI significantly downregulated the expressions of IL-5, IL-13, TNFα, TSLP, IL-1β and IL-6 (p < 0.05). Administration of TBI caused a marked reduction in OVA-mediated increase in caspase-1 activity in mice intranasal tissues, and also significantly reduced OVA-induced excessive production of MIP-2 and ICAM-1 (p < 0.05). Moreover, TBI prevented OVA-induced infiltration of eosinophils and mast cells into intranasal tissues (p < 0.05). Conclusion: TBI reduces levels of IgE and various pro-inflammatory cytokines in OVA-administered mice. It also regulates Th1:Th2 ratio, inhibited activity of caspase-1, suppressed mast cell/eosinophil infiltration and reduced ICAM-1 and MIP-2 levels. Therefore, TBI possesses inhibitory potential against rhinitis allergy, and thus can potentially be developed as a new treatment strategy for asthma. Keywords: Trifluorobenzamidine, Anti-inflammation, Allergic rhinitis, Cytokines, Caspase-1, Itching

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Non-canonical Caspase-1 Signaling Drives RIP2-Dependent and TNF-α-Mediated Inflammation In Vivo

Cell Reports ◽

10.1016/j.celrep.2020.01.090 ◽

2020 ◽

Vol 30 (8) ◽

pp. 2501-2511.e5 ◽

Cited By ~ 2

Author(s):

Sören Reinke ◽

Mary Linge ◽

Hans H. Diebner ◽

Hella Luksch ◽

Silke Glage ◽

...

Keyword(s):

Caspase 1 ◽

Tnf Α

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Shiga Toxins Activate the NLRP3 Inflammasome Pathway To Promote Both Production of the Proinflammatory Cytokine Interleukin-1β and Apoptotic Cell Death

Infection and Immunity ◽

10.1128/iai.01095-15 ◽

2015 ◽

Vol 84 (1) ◽

pp. 172-186 ◽

Cited By ~ 28

Author(s):

Moo-Seung Lee ◽

Haenaem Kwon ◽

Eun-Young Lee ◽

Dong-Jae Kim ◽

Jong-Hwan Park ◽

...

Keyword(s):

Cell Death ◽

Nlrp3 Inflammasome ◽

Apoptotic Cell ◽

Apoptotic Cell Death ◽

Interleukin 1Β ◽

Dependent Manner ◽

Shiga Toxins ◽

Caspase 1 ◽

Immune Signaling Pathway ◽

Tnf Α

Shiga toxin (Stx)-mediated immune responses, including the production of the proinflammatory cytokines tumor necrosis-α (TNF-α) and interleukin-1β (IL-1β), may exacerbate vascular damage and accelerate lethality. However, the immune signaling pathway activated in response to Stx is not well understood. Here, we demonstrate that enzymatically active Stx, which leads to ribotoxic stress, triggers NLRP3 inflammasome-dependent caspase-1 activation and IL-1β secretion in differentiated macrophage-like THP-1 (D-THP-1) cells. The treatment of cells with a chemical inhibitor of glycosphingolipid biosynthesis, which suppresses the expression of the Stx receptor globotriaosylceramide and subsequent endocytosis of the toxin, substantially blocked activation of the NLRP3 inflammasome and processing of caspase-1 and IL-1β. Processing and release of both caspase-1 and IL-1β were significantly reduced or abolished in Stx-intoxicated D-THP-1 cells in which the expression of NLRP3 or ASC was stably knocked down. Furthermore, Stx mediated the activation of caspases involved in apoptosis in an NLRP3- or ASC-dependent manner. In Stx-intoxicated cells, the NLRP3 inflammasome triggered the activation of caspase-8/3, leading to the initiation of apoptosis, in addition to caspase-1-dependent pyroptotic cell death. Taken together, these results suggest that Stxs trigger the NLRP3 inflammasome pathway to release proinflammatory IL-1β as well as to promote apoptotic cell death.

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Role of endogenous testosterone in myocardial proinflammatory and proapoptotic signaling after acute ischemia-reperfusion

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00784.2004 ◽

2005 ◽

Vol 288 (1) ◽

pp. H221-H226 ◽

Cited By ~ 70

Author(s):

Meijing Wang ◽

Ben M. Tsai ◽

Ajay Kher ◽

Lauren B. Baker ◽

G. Mathenge Wairiuko ◽

...

Keyword(s):

P38 Mapk ◽

Functional Recovery ◽

Caspase 3 ◽

Diastolic Pressure ◽

Contractile Function ◽

Ischemia Reperfusion ◽

Left Ventricular ◽

Acute Ischemia ◽

Caspase 1 ◽

Tnf Α

Myocardial ischemia is the leading cause of death in both men and women; however, very little information exists regarding the effect of testosterone on the response of myocardium to acute ischemic injury. We hypothesized that testosterone may exert deleterious effects on myocardial inflammatory cytokine production, p38 MAPK activation, apoptotic signaling, and myocardial functional recovery after acute ischemia-reperfusion (I/R). To study this, isolated, perfused rat hearts (Langendorff) from adult males, castrated males, and males treated with a testosterone receptor blocker (flutamide) were subjected to 25 min of ischemia followed by 40 min of reperfusion. Myocardial contractile function (left ventricular developed pressure, left ventricular end-diastolic pressure, positive and negative first derivative of pressure) was continuously recorded. After reperfusion, hearts were analyzed for expression of tissue TNF-α, IL-1β, and IL-6 (ELISA) and activation of p38 MAPK, caspase-1, caspase-3, caspase-11, and Bcl-2 (Western blot). All indices of postischemic myocardial functional recovery were significantly higher in castrated males or flutamide-treated males compared with untreated males. After I/R, castrated male and flutamide-treated male hearts had decreased TNF-α, IL-1β, and IL-6; decreased activated p38 MAPK; decreased caspase-1, caspase-3, and caspase-11; and increased Bcl-2 expression compared with untreated males. These results show that blocking the testosterone receptor (flutamide) or depleting testosterone (castration) in normal males improves myocardial function after I/R. These effects may be attributed to the proinflammatory and/or the proapoptotic properties of endogenous testosterone. Further understanding may allow therapeutic manipulation of sex hormone signaling mechanisms in the treatment of acute I/R.

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Low Energy Shock Wave Therapy Inhibits Inflammatory Molecules and Suppresses Prostatic Pain and Hypersensitivity in a Capsaicin Induced Prostatitis Model in Rats

International Journal of Molecular Sciences ◽

10.3390/ijms20194777 ◽

2019 ◽

Vol 20 (19) ◽

pp. 4777 ◽

Cited By ~ 1

Author(s):

Hung-Jen Wang ◽

Pradeep Tyagi ◽

Yu-Ming Chen ◽

Michael B. Chancellor ◽

Yao-Chi Chuang

Keyword(s):

Shock Wave ◽

Inflammatory Cells ◽

Low Energy ◽

Therapeutic Effects ◽

Inflammatory Reactions ◽

Caspase 1 ◽

Tnf Α ◽

Pain Reaction ◽

Cox 2 ◽

Inflammatory Molecules

The effect of low energy shock wave (LESW) therapy on the changes of inflammatory molecules and pain reaction was studied in a capsaicin (10 mM, 0.1 cc) induced prostatitis model in rats. Intraprostatic capsaicin injection induced a pain reaction, including closing of the eyes, hypolocomotion, and tactile allodynia, which effects were ameliorated by LESW treatment. LESW therapy (2Hz, energy flux density of 0.12 mJ/mm2) at 200 and 300 shocks significantly decreased capsaicin-induced inflammatory reactions, reflected by a reduction of tissue edema and inflammatory cells, COX-2 and TNF-α stained positive cells, however, the therapeutic effects were not observed at 100 shocks treated group. Capsaicin-induced IL-1β, COX-2, IL-6, caspase-1, and NGF upregulation on day 3 and 7, while NALP1 and TNF-α upregulation was observed on day 7. LESW significantly suppressed the expression of IL-1β, COX-2, caspase-1, NGF on day 3 and IL-1β, TNF-α, COX-2, NALP1, caspase-1, NGF expression on day 7 in a dose-dependent fashion. LESW has no significant effect on IL-6 expression. Intraprostatic capsaicin injection activates inflammatory molecules and induces prostatic pain and hypersensitivity, which effects were suppressed by LESW. These findings might be the potential mechanisms of LESW therapy for nonbacterial prostatitis in humans.

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Effects of Joint Lavage with Dimethylsulfoxide on LPS-Induced Synovitis in Horses—Clinical and Laboratorial Aspects

Veterinary Sciences ◽

10.3390/vetsci7020057 ◽

2020 ◽

Vol 7 (2) ◽

pp. 57

Author(s):

Eric Danilo Pauls Sotelo ◽

Cynthia Prado Vendruscolo ◽

Joice Fülber ◽

Sarah Raphaela Torquato Seidel ◽

Fernando Mosquera Jaramillo ◽

...

Keyword(s):

Synovial Fluid ◽

Cartilage Degradation ◽

Cell Counts ◽

Tnf Α ◽

Equine Medicine ◽

Lactated Ringer's Solution ◽

White Blood Cell Counts ◽

Factor Α ◽

Joint Lavage

Several studies in human and equine medicine have produced controversial results regarding the role of dimethylsulfoxide (DMSO) as a therapeutic agent. This study aimed to evaluate the effect of joint lavage with different DMSO concentrations on biomarkers of synovial fluid inflammation and cartilage degradation in joints with lipopolysaccharide (LPS)-induced synovitis. Twenty-six tibiotarsal joints of 13 horses were randomly distributed into four groups (lactated Ringer’s solution; 5% DMSO in lactated Ringer’s; 10% DMSO in lactated Ringer’s; and sham). All animals were evaluated for the presence of lameness, and synovial fluid analyses were performed at 0 h, 1 h, 8 h, 24 h, and 48 h (T0, T1, T8, T24, and T48, respectively). The white blood cell counts (WBC), total protein (TP), urea, prostaglandin E2 (PGE2), interleukin (IL)-1β, IL-6, IL-10, tumor necrosis factor-α (TNF-α), hyaluronic acid (HA), and chondroitin sulfate (CS) concentrations were measured. The WBC counts and PGE2, IL-1β, IL-6, and TP concentrations increased in all groups at T8 compared to baseline values (p < 0.05). At T48, only the 5% DMSO and 10% DMSO groups showed a significant decrease in WBC counts (p < 0.05). Furthermore, the 10% DMSO group had lower concentrations of PGE2 and IL-1β at T48 than at T8 (p < 0.05) and presented lower IL-6 levels than the5% DMSO and lactated Ringer’s groups at T24. All groups showed an increase in CS concentration after LPS-induced synovitis. Joint lavage with 10% DMSO in lactated Ringer’s has anti-inflammatory but not chondroprotective effects.

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