Correlation Engine 2.0
Clear Search sequence regions

  • across (3)
  • CCL20 (2)
  • chemotaxins (1)
  • CXCL1 (1)
  • CXCL3 (1)
  • fibroblasts (7)
  • human (2)
  • ICAM1 (1)
  • IL1RL1 (2)
  • IL33 (7)
  • il33 protein, human (1)
  • il6 (1)
  • il8 (1)
  • interleukin 11 (12)
  • lung (1)
  • lymphocytes (1)
  • MCP1 (1)
  • monocytes (1)
  • neutrophils (1)
  • protein human (1)
  • receptor (1)
  • rna (1)
  • SERPINB2 (1)
  • signal (1)
  • skin (1)
  • STAT3 (2)
  • TNFRSF18 (1)
  • Sizes of these terms reflect their relevance to your search.

    Interleukin 11 (IL11) is upregulated in inflammatory conditions, where it is mostly believed to have anti-inflammatory activity. However, recent studies suggest instead that IL11 promotes inflammation by activating fibroblasts. Here, we assessed whether IL11 is pro- or anti-inflammatory in fibroblasts. Primary cultures of human kidney, lung or skin fibroblasts were stimulated with IL11 that resulted in the transient phosphorylation of signal transducer and activator of transcription 3 (STAT3) and the sustained activation of extracellular signal-regulated protein kinases (ERK). RNA sequencing over a time course of IL11 stimulation revealed a robust but short-lived transcriptional response that was enriched for gene set hallmarks of inflammation and characterized by the upregulation of SERPINB2, TNFRSF18, Interleukin 33 (IL33), CCL20, IL1RL1, CXCL3/5/8, ICAM1 and IL11 itself. IL33 was the most upregulated signaling factor (38-fold, p = 9.8 × 10-5), and IL1RL1, its cognate receptor, was similarly increased (18-fold, p = 1.1 × 10-34). In proteomic studies, IL11 triggered a proinflammatory secretome with the notable upregulation of IL8, IL6, MCP1, CCL20 and CXCL1/5/6, which are important chemotaxins for neutrophils, monocytes, and lymphocytes. IL11 induced IL33 expression across fibroblast types, and the inhibition of STAT3 but not of MEK/ERK prevented this. These data establish IL11 as pro-inflammatory with specific importance for priming the IL33 alarmin response in inflammatory fibroblasts across tissues.


    Anissa A Widjaja, Sonia Chothani, Sivakumar Viswanathan, Joyce Wei Ting Goh, Wei-Wen Lim, Stuart A Cook. IL11 Stimulates IL33 Expression and Proinflammatory Fibroblast Activation across Tissues. International journal of molecular sciences. 2022 Aug 10;23(16)

    Expand section icon Mesh Tags

    Expand section icon Substances

    PMID: 36012165

    View Full Text