Cytokine-Induced JAK2-STAT3 Activates Tissue Regeneration under Systemic or Local Inflammation

We investigated the immune response mechanisms under systemic and local inflammation using mouse models whereby lipopolysaccharide (LPS) was administered intraperitoneally to induce systemic inflammation, and epicutaneous sensitization with ovalbumin was used to induce local inflammation. LPS increased the immune cell infiltration in the cardiac muscle near the aorta, alveoli, hepatic sinusoid, renal interstitium, and the submucosal layer of the duodenum. Similarly, ovalbumin increased the abundance of macrophages in the skin. Both LPS and ovalbumin induced NF-κB p65 and IκBα phosphorylation, as well as the expression of NF-κB target genes (TLR4, IL6, and TNFα). Additionally, both LPS and ovalbumin led to an increase in the absolute IL-1β, IL-6, and TNFα serum levels and cytokine-related janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) phosphorylation. Moreover, the activated JAK2/STAT3 signaling increased the number of Ki67-positive cells (proliferating cells) and development pathway target gene expression (regeneration) in the inflammation models. In conclusion, LPS and ovalbumin increase immune cell infiltration in tissues, NF-κB activation, cytokine levels in serum, cytokine-stimulated JAK2/STAT3 signaling, and tissue regeneration.