Tumor-derived cyclooxygenase-2 fuels hypothalamic inflammation
0303 health sciences
03 medical and health sciences
Life Science
DOI:
10.1016/j.bbi.2024.11.002
Publication Date:
2024-11-04T22:48:09Z
AUTHORS (15)
ABSTRACT
Hypothalamic inflammation often coincides with cancer and cachexia-anorexia. Prior work established the significance of tumor-derived inflammatory factors in triggering hypothalamic inflammation, yet precise mechanisms remained elusive. Here, we demonstrate that prostaglandin E2 (PGE2), produced tumor via cyclooxygenase-2 (COX-2), plays a pivotal role this context. PGE2 itself directly exerts pro-inflammatory effects on hypothalamus through EP4 receptor, while also augmenting NF-κB pathways presence host gut-derived pathogen-associated molecular patterns (PAMPs). In tumor-bearing mice, confirm synergistic interaction between COX-2/PGE2 host-derived lipopolysaccharide (LPS) amplifying inflammation. Supporting mechanism find tumor-specific knockout COX-2 attenuates improves survival mice. Together, these findings highlight tumor-associated fuelling They emphasize potential inhibition targeting gut permeability as novel therapeutic strategy for improving clinical outcomes patients.
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