Interleukin-1 Receptor-Associated Kinase 1/4 as a Novel Target for Inhibiting Neointimal Formation After Carotid Balloon Injury
Cardiovascular System & Cardiology; in-vivo; smooth-muscle-cells; signaling pathways; hyperplasia; NF kappa B; arterial injury; bacterial infections; Carotid artery balloon injury; intimal; irak-4 protein; IRAK1/4; muscle cell; Neointimal formation; NF kappa B; TLR4; toll-like-receptor; toll-like-receptor-4 expression; Vascular smooth
Aim: Interleukin-1 receptor-associated kinase 1 (IRAK1) and IRAK4 play essential roles in the induction of inflammatory gene products. We aimed to investigate the effect of the inhibition of IRAK1 and IRAK4 kinase activities on neointimal formation in rats with carotid artery balloon injuries using the IRAK1/4 inhibitor N-(2-Morpholinylethyl)-2-(3-nitrobenzoylamido)-benzimidazole, a cell-permeable benzimidazole compound. Methods: Wistar rats and vascular smooth muscle cells (VSMCs) isolated from the thoracic aortas were used. Toll-like receptor 4 (TLR4)-mediated nuclear factor kappa B (NF kappa B) signaling pathway was revealed by microarrays analysis. In addition, the differential expression of the TLR4 pathway genes, including TLR4, IRAK1, I kappa B alpha, and interleukin-1 beta (IL-1 beta), was confirmed by quantitative real-time polymerase chain reaction. Immunohistochemical staining, elastic-van Gieson and Masson staining, 5-ethynyl-2'-deoxyuridine staining, enzyme-linked immunosorbent assay, transwell migration assay and western blotting were also contributed for relevant detection. Results: The expression of TLR4 protein gradually increased at days 1, 3, 7, and 21 after balloon injury compared with the uninjured group. The dual inhibition of IRAK1 and IRAK4 attenuated neointimal formation and fibrotic remodeling after injury in vivo and suppressed VSMC proliferation and migration in vitro. The production of mediators such as tumor necrosis factor-alpha and IL-1 beta in injured arteries were also reduced by the inhibition of IRAK1 and IRAK4. The expression of NF kappa B p65- and F4/80-positive cells in inhibitor rats were fewer than those in control rats at day 7, while IRAK1 expression was markedly higher at day 3 in inhibitor rats. Furthermore, western blotting analysis revealed that the IRAK1/4 inhibitor suppressed the IRAK1 and IRAK4 kinase activities and the activation of the TLR4-mediated NF kappa B pathway in vivo and in vitro. Conclusions: This study suggested that IRAK1/4 could serve as a potential therapeutic target to suppress neointimal formation in carotid arteries after balloon injury through the TLR4/NF kappa B signaling pathway.
Bai S R; Li D Y; Zhou Z M; Cao J L; Xu T D; Zhang X T; Wang Y; Guo J S; Zhang Y B
Journal of Atherosclerosis and Thrombosis
2015
2015
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.5551/jat.29421" target="_blank" rel="noreferrer noopener">10.5551/jat.29421</a>
Human zoonotic infections transmitted by dogs and cats.
Animals; Dogs; Cats; Bacterial Infections; Disease Vectors; Ectoparasitic Infestations; Bacterial Infections – Transmission; Ectoparasitic Infestations – Transmission; Helminthiasis – Transmission; Protozoan Infections – Transmission; Zoonoses – Transmission
Tan J S
Archives of Internal Medicine
1997
1997-09-22
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1001/archinte.157.17.1933" target="_blank" rel="noreferrer noopener">10.1001/archinte.157.17.1933</a>
Dental emergencies: infection and nerve blocks... part 2.
Anesthetics; Bacterial Infections; Emergency Care; Facial Nerve; Gingival Diseases; Antibiotics – Administration and Dosage; Local – Administration and Dosage; Mouth Diseases – Complications; Mouth Diseases – Diagnosis; Nerve Block – Methods; Pain – Therapy
Amsterdam J T
Emergency Medicine (00136654)
1994
1994-01
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
ANTIGENIC-STIMULATION AND MULTIPLE-MYELOMA - A PROSPECTIVE-STUDY
inflammation; cancer; association; follow-up; leukemia; Oncology; rheumatoid-arthritis; risk; lymphoma; allergens; Allergy; antigens; autoimmune diseases; bacterial infections; multiple myeloma (etiology); plasma-cell; prospective studies
Background. A causal relationship between antigenic conditions and multiple myeloma was suggested by case reports. Although controlled studies identified associations with individual conditions, they failed to give overall support to the hypothesis. Using a prospective cohort representative of the U.S. population, the authors hypothesized that immune-stimulating conditions are a risk factor for multiple myeloma. Methods. The First National Health and Nutrition Examination Survey cohort of 14,407 persons were interviewed from 1971 to 1975 by the National Center for Health Statistics. Vital status with cause of death and hospitalizations were ascertained from 1982 to 1985 and in 1986. From the initial questionnaire, four risk factors were constructed: allergies (asthma, hives, hay fever, food allergies, and other allergies); autoimmune conditions (arthritis, thyroid disease and/or medication, rheumatic fever, diabetes, pernicious anemia); chronic bacterial conditions (chronic bronchitis or emphysema, chronic cough, tuberculosis, ulcers); and inflammatory conditions (gout, gallstones, recurrent or chronic enteritis, pleurisy). Results. Eighteen multiple myeloma (MM) cases were documented. The rate ratio (RR) of MM increased as the number of reported inflammatory conditions increased (one condition, RR = 2.0, 95% confidence interval [CI] = 1.2-3.3; 2 or more conditions, RR = 4.3, 95% CI = 1.5-12.4). The RR of myeloma also increased (P = 0.0002) with time since start of inflammatory conditions (RR = 1.6 for every 10 years of exposure). When cases were restricted to those with more than five years of follow-up, myeloma risk increased with the number of inflammatory conditions (two conditions, RR = 4.6, 95% CI = 1.5-13.8). Conclusions. Although the number of cases is small and exposure may be misclassified, the prospective nature of the study design strengthens the results of the study.
Bourguet C C; Logue E E
Cancer
1993
1993-10
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1002/1097-0142(19931001)72:7%3C2148::aid-cncr2820720714%3E3.0.co;2-q" target="_blank" rel="noreferrer noopener">10.1002/1097-0142(19931001)72:7%3C2148::aid-cncr2820720714%3E3.0.co;2-q</a>