2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), a heterocyclic amine with strong carcinogenic and mutagenic potential, is created abundantly in the overcooking of meat and fish. Carcinogenic toxicants are often implicated in immunosuppression, where cancer cells are not easily eliminated by the host immune system. Here, we investigated the effect of PhIP on tumor necrosis factor-alpha (TNF-alpha) expression by murine macrophage-like cells (RAW 264.7) stimulated with lipoteichoic acid (LTA), a major virulence factor of Gram-positive bacteria. Upon exposure to LTA purified from Staphylococcus aureus, TNF-alpha expression was substantially induced, whereas pretreatment with PhIP significantly inhibited LTA-induced TNF-alpha expression. LTA is known to activate Toll-like receptor 2 (TLR2) and NF-kappaB, resulting in TNF-alpha expression. Interestingly, PhIP did not interfere with LTA-binding to TLR2, its stimulation of TLR2, or the DNA-binding activity of NF-kappaB. However, treatment with actinomycin D facilitated the PhIP-induced attenuation of TNF-alpha mRNA expression, implying that PhIP might decrease TNF-alpha mRNA stability rather than its biosynthesis. Furthermore, Western blot analysis demonstrated that PhIP reduced the phosphorylation of ERK1/2 and JNK but not p38 kinase in LTA-stimulated cells. The addition of a protein kinase C (PKC) activator, phorbol 12-myristate 13-acetate, rescued PhIP-inhibited TNF-alpha expression in LTA-stimulated cells. These results suggest that PhIP downregulates TNF-alpha expression in LTA-stimulated macrophages by decreasing TNF-alpha mRNA stability and signaling pathways related to PKC, ERK1/2, and JNK activation.
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http://dx.doi.org/10.1016/j.canlet.2008.09.003 | DOI Listing |
World J Urol
January 2025
Department of Urology, Peking University People's Hospital, Beijing, 100044, China.
Purpose: This study aims to elucidate the role of pituitary adenylate cyclase-activating polypeptide (PACAP) in Hunner-type Interstitial Cystitis (HIC) and evaluate its potential as a therapeutic target.
Methods: Bladder tissue samples were obtained from HIC patients and normal bladder tissue from bladder cancer patients. PACAP expression was assessed through immunohistochemistry.
Sci Rep
January 2025
Department of Critical Care Medicine, Tongde Hospital of Zhejiang Province, #234 Gucui Road, Hangzhou, 310012, Zhejiang, People's Republic of China.
The intestinal barrier function is a critical defense mechanism in the human body, serving as both the primary target and initiating organ in cases of sepsis. Preserving the integrity of this barrier is essential for preventing complications and diseases, including sepsis and mortality. Despite this importance, the impact of resveratrol on intestinal barrier function remains unclear.
View Article and Find Full Text PDFFood Chem Toxicol
January 2025
Zoology Department, Faculty of Science, Al-Azhar University, 71524 Assuit, Egypt.
This study aimed to define the antitumor effect of ethanolic extract of Pistacia vera leaves (PEE) toward breast cancer both in vitro and in vivo using dimethyl-benz(a)anthracene (DMBA)-induced breast tumor in adult female rats. PEE showed a potent antioxidant effect toward both DPPH (1,1-diphenyl-2-picrylhydrazyl) and ABTS (2,2'-azino-bis(3-ethylbenzthiazoline-6-sulphonic acid) radicals with IC values of 72.6 and 107.
View Article and Find Full Text PDFNeuroscience
January 2025
Department of Psychiatry, Xijing Hospital, The Fourth Military Medical University, Xi'an, Shaanxi, China. Electronic address:
Background: The mechanisms underlying esketamine's therapeutic effects remain elusive. The study aimed to explore the impact of single esketamine treatment on LPS-induced adolescent depressive-like behaviors and the role of Nrf2 regulated neuroinflammatory response in esketamine-produced rapid antidepressant efficacy.
Methods: Adolescent male C57BL/6J mice were randomly assigned to three groups: control, LPS, and LPS + esketamine (15 mg/kg, i.
J Oral Biosci
January 2025
Division of Cellular Biosignal Sciences, Department of Biochemistry, Iwate Medical University, Yahaba, Iwate, 028-3694, Japan. Electronic address:
Objectives: Temporomandibular joint (TMJ) osteoarthritis (OA) is an inflammatory disease that involves periarthritis of the TMJ and destruction of cartilage tissue in the mandibular condyle. However, the role of proinflammatory cytokines in the expression levels of matrix metalloproteinase (MMP) remains inconclusive. Thus, in this study, we aimed to investigate the effect of proinflammatory cytokines on the expression of MMPs.
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