Immunomodulatory Effects of 17β-Estradiol on Epithelial Cells during Bacterial Infections

Figure 2

Signal transduction pathways of epithelial cells involved in the recognition of pathogenic bacteria. Epithelial cells are part of the innate immune system, which senses the presence of microbial pathogen-associated molecular patterns (PAMPs) present in bacteria. These elements activate inflammatory pathways mainly through the activation of Toll-like receptors (TLRs). TLR proteins are coupled to the scaffold proteins, myeloid differentiation primary response 88 (MyD88), or TIR domain-containing adapter-inducing interferon-β (TRIF), which are associated with interleukin-1 receptor-associated kinase 1/4 (IRAK1/4). This kinase is coupled to TNF receptor-associated factor (TRAF) [38]. TLR signaling results in the downstream activation of the following three major families of proteins important in activating inflammatory gene expression: interferon regulatory factors (IRFs); mitogen-activated protein kinase (MAPK) pathway, such as c-Jun N-terminal kinase (JNK), protein 38 (P38), and extracellular signal-regulated kinases (ERKs); and the canonical inflammatory pathway, namely, nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB). However, other transcriptional factors, such as activator protein 1 (AP-1), can also be activated. Bacteria induces the expression of many inflammatory genes and cytokine secretion, such as interleukin 1-beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) [36]. Intracellular bacteria can be recognized in epithelial cells by TLRs (endosome) or Nod-like receptors (NODs), which can activate the inflammasome. This is a multiprotein complex activated by caspases, and its activation and composition depend on the activator, which initiates inflammasome assembly, resulting in the processing of inflammatory cytokines such as IL-1β and interleukin 18 (IL-18) [63].