IL-1β Augments TNF-α–Mediated Inflammatory Responses from Lung Epithelial Cells

Abstract

Interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) mediate the development of numerous inflammatory lung diseases. Since IL-1β is typically activated in situations where TNF-α is produced, it was hypothesized that IL-1β alters TNF-α-induced proinflammatory epithelial cell function by altering TNF receptor shedding and surface abundance. In this study, the impact of IL-1β on TNF-α-mediated chemokine production as well as TNF receptor surface expression and shedding were investigated from mouse pulmonary epithelial cells (MLE-15). Interleukin-1β rapidly and persistently enhanced soluble and surface TNFR2. These effects were dependent on TNFR1 expression. TNFR2 small-interfering RNA (siRNA) shifted IL-1β responses, significantly increasing surface and shed TNFR1 implying IL-1β selectively modifies TNF receptors depending on cellular receptor composition. mRNA expression of both receptors was unaltered by IL-1β up to 24 h or in combination with TNF-α indicating effects were post- transcriptional. Interleukin-1β pretreatment enhanced TNF-α-induced macrophage inflammatory protein (MIP)-2 and KC mRNA expression as well as MIP-2 and KC protein levels at the same time point analyzed. Experiments utilizing siRNA against the TNF receptors and a TNFR1 neutralizing antibody demonstrated TNF-α induced MIP-2 through TNFR1 whereas both receptors may have contributed to KC production. These data suggest IL-1β modulates TNF-α–mediated inflammatory lung diseases by enhancing epithelial cell TNF receptor surface expression.

Catalase Enhances Viability of Human Chondrocytes in Culture by Reducing Reactive Oxygen Species and Counteracting Tumor Necrosis Factor-α-Induced Apoptosis

“…Cell apoptosis is evoked by multiple pathways but mainly the intrinsic and extrinsic signaling cascades, both of which result in activation of executor caspases through the initiator caspase Cas-8 [51]. The association of TNF-α with TNFR [12] on the cell surface recruits TRADD, FADD to form the cytosolic platform of DISC as a ligand-dependent transmembrane signaling receptor [52] that initiates inflammation [16] and apoptosis cascade [17,18]. DISC provokes the Cas-8 to activate Cas-3, which sabotages a range of cytoplasmic proteins and dismantles chromatin and nucleoplasmic proteins in the nucleus, eventually resulting in apoptosis.…”

IL-1β and TLR4 Signaling Are Involved in the Aggravated Murine Acute Graft-versus-Host Disease Caused by Delayed Bortezomib Administration

“…Our results suggested that IL-1b could be upstream of TNF-a and TNFR. Most importantly, IL-1b secretion is negatively regulated by NF-kB activity (7,25). During the initial phase of GVHD, pro-IL-1b production is promoted, whereas its processing and secretion are inhibited by the activation of NF-kB through the inhibition of caspase-1 by NF-kB-dependent gene products.…”

“…It was shown that IL-1b could modulate TNF-a-mediated inflammatory lung diseases (24). Moreover, IL-1b secretion was negatively regulated by NF-kB activity (7,25). Therefore, IL-1b could be the cytokine affected directly by delayed bortezomib administration.…”

Complex Immune Cell Interplay in the Gamma Interferon Response during Toxoplasma gondii Infection

“…Furthermore, production of IFN-␥ by SCID mouse splenocytes stimulated with IL-12 plus TNF was completely ablated by administering anti-IL-1␤ (69). As a pleotropic mediator of inflammation, IL-1␤ mediates its protective effects via multiple mechanisms, including enhancing expression of the TNF receptor, which may explain the synergistic effect of IL-1␤ and TNF (70). While TNF alone is unable to significantly increase the antiparasitic activity of macrophages, TNF synergizes with IFN-␥ to enhance it (68).…”