Yan Shuangye, Holt Sam, Gao Xiao, Wilson Joanna B
School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK.
School of Molecular Biosciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
Life Sci Alliance. 2025 Aug 6;8(10). doi: 10.26508/lsa.202403138. Print 2025 Oct.
The human and mouse orthologues / encode a chitinase-related protein that is catalytically inactive. It is overexpressed in multiple inflammatory disorders and cancers and is thought to be pro-inflammatory and immune modulatory, but its role in tumorigenesis is unclear. Nevertheless, it has been proposed as a therapeutic target. To explore this, we have used Chil1 knockout compared with Chil1 WT mice, in combination with a transgenic mouse model (encoding the latent membrane protein-1 of EBV) of carcinoma-prone chronic skin inflammation. The data reveal that although high levels of Chil1 are pro-inflammatory, this can ameliorate the consequent tissue damage. Moreover, although high-level Chil1 promotes carcinoma growth, physiological levels inhibit the formation of papillomatous lesions and similarly inhibit the growth of tumours from transplanted cells. Furthermore, tumours arising in the Chil1 knockout mice showed reduced leukocyte infiltration, consistent with an impaired anti-tumour response. These dual roles warrant caution in developing and exploring therapeutic drugs that might abrogate Chil1 expression or effect.
人类和小鼠的直系同源基因编码一种催化无活性的几丁质酶相关蛋白。它在多种炎症性疾病和癌症中过表达，被认为具有促炎和免疫调节作用，但其在肿瘤发生中的作用尚不清楚。尽管如此，它已被提议作为一个治疗靶点。为了探究这一点，我们使用了Chil1基因敲除小鼠与Chil1野生型小鼠进行比较，并结合了一个易患癌症的慢性皮肤炎症转基因小鼠模型（编码EBV的潜伏膜蛋白-1）。数据显示，虽然高水平的Chil1具有促炎作用，但这可以减轻随之而来的组织损伤。此外，虽然高水平的Chil1促进癌生长，但生理水平的Chil1会抑制乳头状瘤病变的形成，同样也会抑制移植细胞形成的肿瘤的生长。此外，Chil1基因敲除小鼠中出现的肿瘤显示白细胞浸润减少，这与抗肿瘤反应受损一致。这些双重作用警示在开发和探索可能消除Chil1表达或作用的治疗药物时需谨慎。
