scholarly journals Inflammation and Wnt Signaling: Target for Immunomodulatory Therapy?

Author(s):  
Imen Jridi ◽  
Kirsten Canté-Barrett ◽  
Karin Pike-Overzet ◽  
Frank J. T. Staal

Wnt proteins comprise a large family of highly conserved glycoproteins known for their role in development, cell fate specification, tissue regeneration, and tissue homeostasis. Aberrant Wnt signaling is linked to developmental defects, malignant transformation, and carcinogenesis as well as to inflammation. Mounting evidence from recent research suggests that a dysregulated activation of Wnt signaling is involved in the pathogenesis of chronic inflammatory diseases, such as neuroinflammation, cancer-mediated inflammation, and metabolic inflammatory diseases. Recent findings highlight the role of Wnt in the modulation of inflammatory cytokine production, such as NF-kB signaling and in innate defense mechanisms as well as in the bridging of innate and adaptive immunity. This sparked the development of novel therapeutic treatments against inflammatory diseases based on Wnt modulation. Here, we summarize the role and function of the Wnt pathway in inflammatory diseases and focus on Wnt signaling as underlying master regulator of inflammation that can be therapeutically targeted.

2017 ◽  
Vol 114 (7) ◽  
pp. 1649-1654 ◽  
Author(s):  
Jesung Moon ◽  
Huanyu Zhou ◽  
Li-shu Zhang ◽  
Wei Tan ◽  
Ying Liu ◽  
...  

The secreted Wnt signaling molecules are essential to the coordination of cell-fate decision making in multicellular organisms. In adult animals, the secreted Wnt proteins are critical for tissue regeneration and frequently contribute to cancer. Small molecules that disable the Wnt acyltransferase Porcupine (Porcn) are candidate anticancer agents in clinical testing. Here we have systematically assessed the effects of the Porcn inhibitor (WNT-974) on the regeneration of several tissue types to identify potentially unwanted chemical effects that could limit the therapeutic utility of such agents. An unanticipated observation from these studies is proregenerative responses in heart muscle induced by systemic chemical suppression of Wnt signaling. Using in vitro cultures of several cell types found in the heart, we delineate the Wnt signaling apparatus supporting an antiregenerative transcriptional program that includes a subunit of the nonfibrillar collagen VI. Similar to observations seen in animals exposed to WNT-974, deletion of the collagen VI subunit, COL6A1, has been shown to decrease aberrant remodeling and fibrosis in infarcted heart tissue. We demonstrate that WNT-974 can improve the recovery of heart function after left anterior descending coronary artery ligation by mitigating adverse remodeling of infarcted tissue. Injured heart tissue exposed to WNT-974 exhibits decreased scarring and reduced Col6 production. Our findings support the development of Porcn inhibitors as antifibrotic agents that could be exploited to promote heart repair following injury.


2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Carol A. de la Motte ◽  
Sean P. Kessler

Hyaluronan is an abundant extracellular matrix component prevalent in the vertebrate intestinal tract. Here we discuss what is known about hyaluronan distribution during homeostasis and inflammatory diseases of the gut and discuss ways in which this glycosaminoglycan can participate in regulating innate host defense mechanisms. These natural responses include mechanisms promoting rapid leukocyte recruitment after bacterial challenge/colon tissue damage as well as promoting epithelial defense mechanisms in the intestine.


2019 ◽  
Vol 4 (1) ◽  
pp. 59-76 ◽  
Author(s):  
Alison E. Fowler ◽  
Rebecca E. Irwin ◽  
Lynn S. Adler

Parasites are linked to the decline of some bee populations; thus, understanding defense mechanisms has important implications for bee health. Recent advances have improved our understanding of factors mediating bee health ranging from molecular to landscape scales, but often as disparate literatures. Here, we bring together these fields and summarize our current understanding of bee defense mechanisms including immunity, immunization, and transgenerational immune priming in social and solitary species. Additionally, the characterization of microbial diversity and function in some bee taxa has shed light on the importance of microbes for bee health, but we lack information that links microbial communities to parasite infection in most bee species. Studies are beginning to identify how bee defense mechanisms are affected by stressors such as poor-quality diets and pesticides, but further research on this topic is needed. We discuss how integrating research on host traits, microbial partners, and nutrition, as well as improving our knowledge base on wild and semi-social bees, will help inform future research, conservation efforts, and management.


2020 ◽  
Vol 4 (3) ◽  
pp. 167-178
Author(s):  
Zurayna Sari

ABSTRAKPelabuhan berperan sebagai fasilitas penunjang pusat pertumbuhan regional dalam proses pembangunan ekonomi wilayah. Pelabuhan Bebas Sabang diarahkan sebagai pusat pertumbuhan ekonomi regional dan diharapkan dapat meningkatkan perekonomian Kawasan Sabang. Permasalahan yang dihadapi Pelabuhan Bebas Sabang adalah belum optimalnya peran dan fungsi Pelabuhan Bebas Sabang dalam menunjang perekonomian wilayah. Penelitian ini bertujuan untuk mengetahui peran Pelabuhan Bebas Sabang dalam mendorong perkembangan perekonomian Kawasan Sabang. Lingkup materi yang dibahas mencakup peran-peran Pelabuhan Bebas Sabang, menentukan potensi dan masalah serta upaya-upaya peningkatan peran Pelabuhan Bebas Sabang. Metode analisis yang dilakukan adalah analisis deskriptif dengan pendekatan analisis data kualitatif dan kuantitatif. Alat analisis yang digunakan adalah analisis SWOT IFAS-EFAS. Hasil analisis menunjukkan dalam kurun waktu 4 (empat) tahun terakhir dari tahun 2010-2013, Pelabuhan Bebas Sabang belum optimal dalam menjalankan perannya, sehingga membutuhkan strategi pengembangan dengan pendekatan Agressive Maintenance Strategy (strategi perbaikan agresif), yaitu strategi konsolidasi internal dengan memperbaiki faktor-faktor kelemahan untuk memaksimalkan pemanfaatan peluang.Kata kunci: Pengelolaan, SWOT IFAS-EFAS, WilayahABSTRACTPort was supporting facility of regional growth center in the process of regional economic development. Sabang free port was directed as the center of regional economic growth and expected to raise the economy of sabang. Problems faced by sabang free port was yet optimal role and function in supporting the economy of the region. This study aimed to determine the role of sabang free port in supporting the economic development of sabang. The covered material scope included roles of sabang free port, determining the potentials and problems and efforts of increasing the role of sabang free port. The method of analysis was descriptive analysis with qualitative and quantitative approach. The analytical tool used was the swot ifas-efas analysis. The analysis results showed in the period of 4 (four) years from 2010 until 2013, sabang free port was not optimal in carrying out its role yet, so it requires development strategies with agressive maintenance strategy approach, which is internal consolidation strategy by improving vulnerability factors to maximize the utilization of opportunities.Keywords:, Management, Regional, SWOT IFAS-EFAS


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