Lnc-ing inflammation to disease

2017 ◽  
Vol 45 (4) ◽  
pp. 953-962 ◽  
Author(s):  
Loretta Magagula ◽  
Maria Gagliardi ◽  
Jerolen Naidoo ◽  
Musa Mhlanga

Termed ‘master gene regulators’ long ncRNAs (lncRNAs) have emerged as the true vanguard of the ‘noncoding revolution’. Functioning at a molecular level, in most if not all cellular processes, lncRNAs exert their effects systemically. Thus, it is not surprising that lncRNAs have emerged as important players in human pathophysiology. As our body's first line of defense upon infection or injury, inflammation has been implicated in the etiology of several human diseases. At the center of the acute inflammatory response, as well as several pathologies, is the pleiotropic transcription factor NF-κβ. In this review, we attempt to capture a summary of lncRNAs directly involved in regulating innate immunity at various arms of the NF-κβ pathway that have also been validated in human disease. We also highlight the fundamental concepts required as lncRNAs enter a new era of diagnostic and therapeutic significance.

2015 ◽  
Vol 62 (3) ◽  
pp. 491-498 ◽  
Author(s):  
Agata Grzywacz ◽  
Joanna Gdula-Argasińska ◽  
Bożena Muszyńska ◽  
Małgorzata Tyszka-Czochara ◽  
Tadeusz Librowski ◽  
...  

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Mireille A. Boink ◽  
Sanne Roffel ◽  
Kamran Nazmi ◽  
Jan G. M. Bolscher ◽  
Enno C. I. Veerman ◽  
...  

Even though skin and oral mucosae are continuously in contact with commensal and opportunistic microorganisms, they generally remain healthy and uninflamed. Host defense peptides (HDPs) make up the body’s first line of defense against many invading pathogens and are involved in the orchestration of innate immunity and the inflammatory response. In this study, we investigated the effect of two salivary HDPs, LL-37 and Hst1, on the inflammatory and antimicrobial response by skin and oral mucosa (gingiva) keratinocytes and fibroblasts. The potent antimicrobial chemokine CCL20 was investigated and compared with chemokines CCL2, CXCL1, CXCL8, and CCL27 and proinflammatory cytokines IL-1αand IL-6. Keratinocyte-fibroblast cocultures showed a synergistic increase in CCL20 secretion upon Hst1 and LL-37 exposure compared to monocultures. These cocultures also showed increased IL-6, CXCL1, CXCL8, and CCL2 secretion, which was IL-1αdependent. Secretion of the antimicrobial chemokine CCL20 was clearly IL-1αindependent. These results indicate that salivary peptides can stimulate skin as well as gingiva cells to secrete antimicrobial chemokines as part of the hosts’ defense to counteract infection.


Blood ◽  
2016 ◽  
Vol 128 (19) ◽  
pp. 2327-2337 ◽  
Author(s):  
Bernd Uhl ◽  
Yannick Vadlau ◽  
Gabriele Zuchtriegel ◽  
Katharina Nekolla ◽  
Kariem Sharaf ◽  
...  

Key Points Aged neutrophils exhibit a distinct, highly reactive phenotype that depends on age-related changes in their molecular repertoire. This specific phenotype of aged neutrophils enables them to serve as “first responders” in inflammatory reactions.


Cancers ◽  
2021 ◽  
Vol 13 (6) ◽  
pp. 1299
Author(s):  
Yi Wu ◽  
Peng Huang ◽  
Xian-Ping Dong

Ca2+ is pivotal intracellular messenger that coordinates multiple cell functions such as fertilization, growth, differentiation, and viability. Intracellular Ca2+ signaling is regulated by both extracellular Ca2+ entry and Ca2+ release from intracellular stores. Apart from working as the cellular recycling center, the lysosome has been increasingly recognized as a significant intracellular Ca2+ store that provides Ca2+ to regulate many cellular processes. The lysosome also talks to other organelles by releasing and taking up Ca2+. In lysosomal Ca2+-dependent processes, autophagy is particularly important, because it has been implicated in many human diseases including cancer. This review will discuss the major components of lysosomal Ca2+ stores and their roles in autophagy and human cancer progression.


Viruses ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 567
Author(s):  
Renate König ◽  
Carsten Münk

In this Special Issue, a wide variety of original and review articles provide a timely overview of how viruses are recognized by and evade from cellular innate immunity, which represents the first line of defense against viruses [...]


2001 ◽  
Vol 280 (6) ◽  
pp. G1197-G1208 ◽  
Author(s):  
Eva Vaquero ◽  
Ilya Gukovsky ◽  
Vjekoslav Zaninovic ◽  
Anna S. Gukovskaya ◽  
Stephen J. Pandol

Transcription factor nuclear factor-κB (NF-κB) is activated in cerulein pancreatitis and mediates cytokine expression. The role of transcription factor activation in other models of pancreatitis has not been established. Here we report upregulation of NF-κB and inflammatory molecules, and their correlation with local pancreatic injury, in a model of severe pancreatitis. Rats received intraductal infusion of taurocholate or saline, and the pancreatic head and tail were analyzed separately. NF-κB and activator protein-1 (AP-1) activation were assessed by gel shift assay, and mRNA expression of interleukin-6, tumor necrosis factor-α, KC, monocyte chemoattractant protein-1, and inducible nitric oxide synthase was assessed by semiquantitative RT-PCR. Morphological damage and trypsin activation were much greater in the pancreatic head than tail, in parallel with a stronger activation of NF-κB and cytokine mRNA. Saline infusion mildly affected these parameters. AP-1 was strongly activated in both pancreatic segments after either taurocholate or saline infusion. NF-κB inhibition with N-acetylcysteine ameliorated the local inflammatory response. Correlation between localized NF-κB activation, cytokine upregulation, and tissue damage suggests a key role for NF-κB in the development of the inflammatory response of acute pancreatitis.


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