Italian researchers have provided further evidence supporting the role of long pentraxin 3 (PTX3) in idiopathic pulmonary fibrosis (IPF). The article, published in Frontiers in Immunology, showed that PTX3 was down-regulated in lung samples taken from IPF patients.
The study also corroborated previous results in mice showing that PTX3 plays a protective and regulatory role during lung injury induced by bleomycin (BLM). Preliminary results in mice also showed that a single administration of PTX3 after BLM injury led to increased survival in PTX3-deficient mice (Ptx3-/-) as well as a weak effect in wild-type (WT) mice.
The authors stated, “Based on the literature and recent data, we propose that PTX3 may have a physiological and protective role during IPF, interacting with various circuits and representing a potential therapeutic target, acting as a pro-resolutive molecule in the context of pulmonary fibrosis.”
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PTX3 is a pattern recognition molecule that plays a role in humoral innate immunity and normal wound healing. In previous research, PTX3 has been found to be localized to fibrotic areas and is associated with sites of macrophage infiltration and collagen deposition. Increasing levels of PTX3 also appear to be temporarily associated with increased expression of M2-macrophage genes.
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The study analyzed microarray data from IPF patient lung samples and found upregulation in genes associated with fibrosis, increased expression of M2-macrophages, and inhibition of M1-macrophages. Analyses also found down-regulation of IL-10 and PTX3 in the samples. The authors stated that these results may indicate that the down-regulation of PTX3 is part of the TGF-β1 regulatory pathway to inhibit fibrinolysis and increase the deposition of extracellular matrix proteins.
The authors also investigated the effects of BLM instillation on WT and Ptx3-/- mice. The results showed that the PTX3-deficient mice had reduced survival and increased weight loss, compared to WT mice, after BLM exposure. The Ptx3-/- mice also had increased lung hemorrhaging and fibrosis compared to the WT animals. Preliminary therapeutic testing of a single 50µg intraperitoneal injection in the animal model one day after BLM instillation increased the survival and decreased the weight loss of Ptx3-/- mice, with a weak effect on survival of WT animals.
Further research needs to be performed but these findings indicate that PTX3 could be a potential therapeutic molecule for IPF.
Reference
Doni A, Mantovani A, Bottazzi B, Russo RC. PTX3 regulation of inflammation, hemostatic response, tissue repair, and resolution of fibrosis favors a role in limiting idiopathic pulmonary fibrosis. Front Immunol. 2021;12:676702. doi:10.3389/fimmu.2021.676702
