Interleukin-1β Attenuates Myofibroblast Formation and Extracellular Matrix Production in Dermal and Lung Fibroblasts Exposed to Transforming Growth Factor-β1

Fibrosis is a condition that can affect nearly every organ in the body, from the kidneys and liver to the lungs and skin. Since this condition is so prevalent, quite a bit of attention has been paid to its pathology and to understanding its physiology. Because of this, researchers have been able to glean several conclusions about the way fibrosis develops and what contributes to its proliferation. For example, IL1β has been seen to be crucial to the development of fibrosis, acting as a mediator. Researchers have also been able to identify the excessive accumulation of extracellular matrix (ECM) as key to the pathology of fibrosis, especially due to an imbalance between collagen synthesis and degradation. Additionally, fibrosis is thought to be brought on by the activation of fibroblasts into myofibroblasts through the excessive deposition of ECM in fibrosis. While all this is known about the condition, the ways in which these different mechanisms interact is still unclear, and leads to some hesitation as to how to proceed in the search for an effective treatment. It is generally understood that IL1β influences the severity of fibrosis, and that reducing it helps to mitigate while increasing it amplifies its severity. However, little is known about how IL1β directly affects fibroblasts, nor has much work been done to confirm the role transforming growth factor-β (such as TGFβ1) in differentiating fibroblasts into myofibroblasts.

This was the focus of the study conducted by Mia et al. from the University of Gronigen in The Netherlands. They wanted to look at the effects of IL1β and TGFβ1, and the combination of the two, on fibroblasts and their transition to myofibroblasts. Since myofibroblasts are partially characterized by an excessive production of collagen, essential to this study was the monitoring of the different substances that go into this process, namely the enzyme lysyl oxidase (LOX). To do this, the research team used the Amplite Fluorimetric Lysyl Oxidase Assay Kit, which uses a proprietary LOX substrate that releases hydrogen peroxide upon LOX oxidation. This allows for the generation of a vibrant fluorescence facilitating the careful and accurate measurement of LOX activity. This method also allows for the detection of sub ng/mL LOX, making it far more sensitive than other assay kits and also eliminating unwanted interference, increasing the reliability of the results.

What Mia et al. found in this study was quite surprising, and is sure to contribute significantly to the current understanding of fibrosis and its pathology. They found that IL1β counteracts a central process in fibrogenesis, namely the TGFβ1-mediated transition of fibroblasts into myofibroblasts. This indicates that, perhaps, the role of IL1β in fibrosis is not as clear as it previously was. Surprising results like this may end up posing more questions than they answer, but are vital for making genuine advancements. By relying on the accuracy of the Amplite Fluorimetric Lysyl Oxidase Assay Kit, the research team was able to produce quality, accurate results that, although unexpected, offer a fantastic contribution to the understanding of fibrosis development.

References

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1. Mia, Masum M., Miriam Boersema, and Ruud A. Bank. "Interleukin-1β attenuates myofibroblast formation and extracellular matrix production in dermal and lung fibroblasts exposed to transforming growth factor-β1." PLoS One 9.3 (2014): e91559.