{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T18:20:37Z","timestamp":1771266037924,"version":"3.50.1"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T00:00:00Z","timestamp":1616457600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006197","name":"Fonden til L\u00e6gevidenskabens Fremme","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100006197","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009708","name":"Novo Nordisk Fonden","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009708","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Chemotherapy-induced gastrointestinal toxicity (CIGT) is a frequent, severe and dose-limiting side effect. Few treatments have proven effective for CIGT. CIGT is characterized by activation of the nuclear factor kappa B pathway which, leads to upregulation of proinflammatory cytokines. The innate immune protein peptidoglycan recognition peptide 2 (PGLYRP2) binds to and hydrolyzes microbial peptidoglycan. Expression of <jats:italic>PGLYRP2<\/jats:italic> is upregulated in the intestine of chemotherapy-treated piglets. In this experimental study, we investigated the role of <jats:italic>Pglyrp2<\/jats:italic> in the development and severity of murine CIGT.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold><jats:italic>Pglyrp2<\/jats:italic> wildtype and <jats:italic>Pglyrp2<\/jats:italic> knockout mice received intraperitoneal injections of chemotherapy (Doxorubicin 20 mg\/kg) to induce CIGT. Weight was monitored daily, and animals were euthanized after 2 or 7 days. Expression of proinflammatory cytokines in the jejunum was measured by quantitative real-time polymerase-chain reaction and enzyme-linked immunosorbent assay. Villus height, crypt depth, and histologic inflammation were evaluated on haematoxylin and eosin stained tissue specimens.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Chemotherapeutic treatment induced weight loss (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), shortening of the small intestine (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), elongation of villus height (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), increased crypt depth (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), and led to elevated mRNA levels of <jats:italic>II1\u03b2<\/jats:italic> (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), <jats:italic>II6<\/jats:italic> (<jats:italic>p<\/jats:italic> &amp;lt; 0.05), and <jats:italic>Tnf<\/jats:italic> (<jats:italic>p<\/jats:italic> &amp;lt; 0.001) at day 2. Protein levels of IL1\u03b2, IL6, and TNF\u03b1 did not change after exposure to chemotherapy. Doxorubicin treated wildtype mice had a more pronounced weight loss compared to knockout mice from day 3 to day 7 (D3-D6: <jats:italic>p<\/jats:italic> &amp;lt; 0.05 and D7: <jats:italic>p<\/jats:italic> &amp;lt; 0.01). No other phenotypic differences were detected.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold><jats:italic>Pglyrp2<\/jats:italic> aggravates chemotherapy-induced weight loss but does not induce a specific pattern of inflammation and morphological changes in the small intestine.<\/jats:p>","DOI":"10.3389\/fonc.2021.635005","type":"journal-article","created":{"date-parts":[[2021,3,23]],"date-time":"2021-03-23T06:39:26Z","timestamp":1616481566000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Peptidoglycan Recognition Peptide 2 Aggravates Weight Loss in a Murine Model of Chemotherapy-Induced Gastrointestinal Toxicity"],"prefix":"10.3389","volume":"11","author":[{"given":"Ann-Sophie","family":"Bech","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anders 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