Warning: Undefined variable $zfal in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Deprecated: str_replace(): Passing null to parameter #3 ($subject) of type array|string is deprecated in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 525
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 530
free
Warning: Undefined variable $sterm in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 531
free free
Warning: file_get_contents(http://eutils.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&id=24172847&cmd=llinks): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
in C:\Inetpub\vhosts\kidney.de\httpdocs\mlpefetch.php on line 445
English Wikipedia
Nephropedia Template TP (
Twit Text
DeepDyve Pubget Overpricing |
lüll IL-1alpha released from damaged epithelial cells is sufficient and essential to trigger inflammatory responses in human lung fibroblasts Suwara MI; Green NJ; Borthwick LA; Mann J; Mayer-Barber KD; Barron L; Corris PA; Farrow SN; Wynn TA; Fisher AJ; Mann DAMucosal Immunol 2014[May]; 7 (3): 684-93Activation of the innate immune system plays a key role in exacerbations of chronic lung disease, yet the potential role of lung fibroblasts in innate immunity and the identity of epithelial danger signals (alarmins) that may contribute to this process are unclear. The objective of the study was to identify lung epithelial-derived alarmins released during endoplasmic reticulum stress (ER stress) and oxidative stress and evaluate their potential to induce innate immune responses in lung fibroblasts. We found that treatment of primary human lung fibroblasts (PHLFs) with conditioned media from damaged lung epithelial cells significantly upregulated interleukin IL-6, IL-8, monocyte chemotactic protein-1, and granulocyte macrophage colony-stimulating factor expression (P<0.05). This effect was reduced with anti-IL-1alpha or IL-1Ra but not anti-IL-1beta antibody. Costimulation with a Toll-like receptor 3 ligand, polyinosinic-polycytidylic acid (poly I:C), significantly accentuated the IL-1alpha-induced inflammatory phenotype in PHLFs, and this effect was blocked with inhibitor of nuclear factor kappa-B kinase subunit beta and TGFbeta-activated kinase-1 inhibitors. Finally, Il1r1-/- and Il1a-/- mice exhibit reduced bronchoalveolar lavage (BAL) neutrophilia and collagen deposition in response to bleomycin treatment. We conclude that IL-1alpha plays a pivotal role in triggering proinflammatory responses in fibroblasts and this process is accentuated in the presence of double-stranded RNA. This mechanism may be important in the repeated cycles of injury and exacerbation in chronic lung disease.|Animals[MESH]|Cell Line[MESH]|Cells, Cultured[MESH]|Culture Media, Conditioned/pharmacology[MESH]|Cytokines/metabolism[MESH]|Disease Models, Animal[MESH]|Endoplasmic Reticulum Stress[MESH]|Epithelial Cells/*metabolism/pathology[MESH]|Fibroblasts/drug effects/*metabolism[MESH]|Humans[MESH]|Inflammation Mediators/metabolism[MESH]|Interleukin-1alpha/genetics/*metabolism[MESH]|Mice[MESH]|Mice, Knockout[MESH]|NF-kappa B/metabolism[MESH]|Oxidative Stress[MESH]|Phenotype[MESH]|Pneumonia/drug therapy/genetics/*metabolism/pathology[MESH]|Receptors, Interleukin-1 Type I/genetics/metabolism[MESH]|Signal Transduction[MESH] |